---
_id: '14378'
abstract:
- lang: eng
  text: 'Branching morphogenesis is a ubiquitous process that gives rise to high exchange
    surfaces in the vasculature and epithelial organs. Lymphatic capillaries form
    branched networks, which play a key role in the circulation of tissue fluid and
    immune cells. Although mouse models and correlative patient data indicate that
    the lymphatic capillary density directly correlates with functional output, i.e.,
    tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms
    ensuring efficient tissue coverage remain poorly understood. Here, we use the
    mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing,
    genetic perturbations, whole-organ reconstructions and theoretical modeling to
    show that the dermal lymphatic capillaries tile space in an optimal, space-filling
    manner. This coverage is achieved by two complementary mechanisms: initial tissue
    invasion provides a non-optimal global scaffold via self-organized branching morphogenesis,
    while VEGF-C dependent side-branching from existing capillaries rapidly optimizes
    local coverage by directionally targeting low-density regions. With these two
    ingredients, we show that a minimal biophysical model can reproduce quantitatively
    whole-network reconstructions, across development and perturbations. Our results
    show that lymphatic capillary networks can exploit local self-organizing mechanisms
    to achieve tissue-scale optimization.'
acknowledgement: "We thank Dr. Kari Alitalo (University of Helsinki and Wihuri Research
  Institute) for critical reading of the manuscript, providing Vegfc+/− and Clp24ΔEC
  mouse strains and for hosting K.V.’s Academy of Finland postdoctoral researcher
  period (2015–2018). We thank Dr. Sara Wickström (University of Helsinki and Wihuri
  Research Institute) for providing Sox9:Egfp mouse\r\nstrain and the discussions.
  We thank Maija Atuegwu and Tapio Tainola for technical assistance. This work received
  funding from the Academy of Finland (K.V., 315710), Sigrid Juselius Foundation (K.V.),
  University of Helsinki (K.V.), Wihuri Research Institute (K.V.), the ERC under the
  European Union’s Horizon 2020 research and innovation program (grant agreement\r\nNo.
  851288 to E.H.) and under the Marie Skłodowska-Curie grant agreement No. 754411
  (to M.C.U.). Part of the work was carried out with the support of HiLIFE Laboratory
  Animal Centre Core Facility, University of Helsinki, Finland. Imaging was performed
  at the Biomedicum Imaging Unit, Helsinki University, Helsinki, Finland, with the
  support of Biocenter Finland. The AAVpreparations were produced at the Helsinki
  Virus (HelVi) Core."
article_number: '5878'
article_processing_charge: Yes
article_type: original
author:
- first_name: Mehmet C
  full_name: Ucar, Mehmet C
  id: 50B2A802-6007-11E9-A42B-EB23E6697425
  last_name: Ucar
  orcid: 0000-0003-0506-4217
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Emmi
  full_name: Tiilikainen, Emmi
  last_name: Tiilikainen
- first_name: Inam
  full_name: Liaqat, Inam
  last_name: Liaqat
- first_name: Emma
  full_name: Jakobsson, Emma
  last_name: Jakobsson
- first_name: Harri
  full_name: Nurmi, Harri
  last_name: Nurmi
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
citation:
  ama: Ucar MC, Hannezo EB, Tiilikainen E, et al. Self-organized and directed branching
    results in optimal coverage in developing dermal lymphatic networks. <i>Nature
    Communications</i>. 2023;14. doi:<a href="https://doi.org/10.1038/s41467-023-41456-7">10.1038/s41467-023-41456-7</a>
  apa: Ucar, M. C., Hannezo, E. B., Tiilikainen, E., Liaqat, I., Jakobsson, E., Nurmi,
    H., &#38; Vaahtomeri, K. (2023). Self-organized and directed branching results
    in optimal coverage in developing dermal lymphatic networks. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-023-41456-7">https://doi.org/10.1038/s41467-023-41456-7</a>
  chicago: Ucar, Mehmet C, Edouard B Hannezo, Emmi Tiilikainen, Inam Liaqat, Emma
    Jakobsson, Harri Nurmi, and Kari Vaahtomeri. “Self-Organized and Directed Branching
    Results in Optimal Coverage in Developing Dermal Lymphatic Networks.” <i>Nature
    Communications</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41467-023-41456-7">https://doi.org/10.1038/s41467-023-41456-7</a>.
  ieee: M. C. Ucar <i>et al.</i>, “Self-organized and directed branching results in
    optimal coverage in developing dermal lymphatic networks,” <i>Nature Communications</i>,
    vol. 14. Springer Nature, 2023.
  ista: Ucar MC, Hannezo EB, Tiilikainen E, Liaqat I, Jakobsson E, Nurmi H, Vaahtomeri
    K. 2023. Self-organized and directed branching results in optimal coverage in
    developing dermal lymphatic networks. Nature Communications. 14, 5878.
  mla: Ucar, Mehmet C., et al. “Self-Organized and Directed Branching Results in Optimal
    Coverage in Developing Dermal Lymphatic Networks.” <i>Nature Communications</i>,
    vol. 14, 5878, Springer Nature, 2023, doi:<a href="https://doi.org/10.1038/s41467-023-41456-7">10.1038/s41467-023-41456-7</a>.
  short: M.C. Ucar, E.B. Hannezo, E. Tiilikainen, I. Liaqat, E. Jakobsson, H. Nurmi,
    K. Vaahtomeri, Nature Communications 14 (2023).
date_created: 2023-10-01T22:01:13Z
date_published: 2023-09-21T00:00:00Z
date_updated: 2023-12-13T12:31:05Z
day: '21'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1038/s41467-023-41456-7
ec_funded: 1
external_id:
  isi:
  - '001075884500007'
  pmid:
  - '37735168'
file:
- access_level: open_access
  checksum: 4fe5423403f2531753bcd9e0fea48e05
  content_type: application/pdf
  creator: dernst
  date_created: 2023-10-03T07:46:36Z
  date_updated: 2023-10-03T07:46:36Z
  file_id: '14384'
  file_name: 2023_NatureComm_Ucar.pdf
  file_size: 8143264
  relation: main_file
  success: 1
file_date_updated: 2023-10-03T07:46:36Z
has_accepted_license: '1'
intvolume: '        14'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Self-organized and directed branching results in optimal coverage in developing
  dermal lymphatic networks
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2023'
...
---
_id: '14426'
abstract:
- lang: eng
  text: To meet the physiological demands of the body, organs need to establish a
    functional tissue architecture and adequate size as the embryo develops to adulthood.
    In the liver, uni- and bipotent progenitor differentiation into hepatocytes and
    biliary epithelial cells (BECs), and their relative proportions, comprise the
    functional architecture. Yet, the contribution of individual liver progenitors
    at the organ level to both fates, and their specific proportion, is unresolved.
    Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage
    tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is
    established (i) fast, (ii) solely by heterogeneous lineage decisions from uni-
    and bipotent progenitors, and (iii) independent of subsequent cell type–specific
    proliferation. Extending lineage tracing to adulthood determined that embryonic
    cells undergo spatially heterogeneous three-dimensional growth associated with
    distinct environments. Strikingly, giant clusters comprising almost half a ventral
    lobe suggest lobe-specific dominant-like growth behaviours. We show substantial
    hepatocyte polyploidy in juveniles representing another hallmark of postembryonic
    liver growth. Our findings uncover heterogeneous progenitor contributions to tissue
    architecture-defining cell type proportions and postembryonic organ growth as
    key mechanisms forming the adult liver.
acknowledgement: "We thank the Ober group for discussion and comments on the manuscript.
  We are grateful to\r\nDr. F. Lemaigre for feedback on the manuscript and Dr. T.
  Piotrowski for invaluable support.\r\nWe thank the department of experimental medicine
  (AEM) in Copenhagen for expert fish\r\ncare. We gratefully acknowledge the DanStem
  Imaging Platform (University of Copenhagen)\r\nfor support and assistance in this
  work.\r\nThis work is supported by Novo Nordisk Foundation grant NNF17CC0027852
  (EAO);\r\nNordisk Foundation grant NNF19OC0058327 (EAO); Novo Nordisk Foundation
  grant\r\nNNF17OC0031204 (PRL); https://novonordiskfonden.dk/en/; Danish National\r\nResearch
  Foundation grant DNRF116 (EAO and AT); https://dg.dk/en/; John and Birthe Meyer\r\nFoundation
  (PRL) and European Research Council (ERC) under the EU Horizon 2020 research and
  Innovation Programme Grant Agreement No. 851288 (EH)."
article_number: e3002315
article_processing_charge: No
article_type: original
author:
- first_name: Iris A.
  full_name: Unterweger, Iris A.
  last_name: Unterweger
- first_name: Julie
  full_name: Klepstad, Julie
  last_name: Klepstad
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Pia R.
  full_name: Lundegaard, Pia R.
  last_name: Lundegaard
- first_name: Ala
  full_name: Trusina, Ala
  last_name: Trusina
- first_name: Elke A.
  full_name: Ober, Elke A.
  last_name: Ober
citation:
  ama: Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA. Lineage
    tracing identifies heterogeneous hepatoblast contribution to cell lineages and
    postembryonic organ growth dynamics. <i>PLoS Biology</i>. 2023;21(10). doi:<a
    href="https://doi.org/10.1371/journal.pbio.3002315">10.1371/journal.pbio.3002315</a>
  apa: Unterweger, I. A., Klepstad, J., Hannezo, E. B., Lundegaard, P. R., Trusina,
    A., &#38; Ober, E. A. (2023). Lineage tracing identifies heterogeneous hepatoblast
    contribution to cell lineages and postembryonic organ growth dynamics. <i>PLoS
    Biology</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pbio.3002315">https://doi.org/10.1371/journal.pbio.3002315</a>
  chicago: Unterweger, Iris A., Julie Klepstad, Edouard B Hannezo, Pia R. Lundegaard,
    Ala Trusina, and Elke A. Ober. “Lineage Tracing Identifies Heterogeneous Hepatoblast
    Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS
    Biology</i>. Public Library of Science, 2023. <a href="https://doi.org/10.1371/journal.pbio.3002315">https://doi.org/10.1371/journal.pbio.3002315</a>.
  ieee: I. A. Unterweger, J. Klepstad, E. B. Hannezo, P. R. Lundegaard, A. Trusina,
    and E. A. Ober, “Lineage tracing identifies heterogeneous hepatoblast contribution
    to cell lineages and postembryonic organ growth dynamics,” <i>PLoS Biology</i>,
    vol. 21, no. 10. Public Library of Science, 2023.
  ista: Unterweger IA, Klepstad J, Hannezo EB, Lundegaard PR, Trusina A, Ober EA.
    2023. Lineage tracing identifies heterogeneous hepatoblast contribution to cell
    lineages and postembryonic organ growth dynamics. PLoS Biology. 21(10), e3002315.
  mla: Unterweger, Iris A., et al. “Lineage Tracing Identifies Heterogeneous Hepatoblast
    Contribution to Cell Lineages and Postembryonic Organ Growth Dynamics.” <i>PLoS
    Biology</i>, vol. 21, no. 10, e3002315, Public Library of Science, 2023, doi:<a
    href="https://doi.org/10.1371/journal.pbio.3002315">10.1371/journal.pbio.3002315</a>.
  short: I.A. Unterweger, J. Klepstad, E.B. Hannezo, P.R. Lundegaard, A. Trusina,
    E.A. Ober, PLoS Biology 21 (2023).
date_created: 2023-10-15T22:01:10Z
date_published: 2023-10-04T00:00:00Z
date_updated: 2023-10-16T07:25:48Z
day: '04'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1371/journal.pbio.3002315
ec_funded: 1
file:
- access_level: open_access
  checksum: 40a2b11b41d70a0e5939f8a52b66e389
  content_type: application/pdf
  creator: dernst
  date_created: 2023-10-16T07:20:49Z
  date_updated: 2023-10-16T07:20:49Z
  file_id: '14431'
  file_name: 2023_PloSBiology_Unterweger.pdf
  file_size: 6193110
  relation: main_file
  success: 1
file_date_updated: 2023-10-16T07:20:49Z
has_accepted_license: '1'
intvolume: '        21'
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: PLoS Biology
publication_identifier:
  eissn:
  - 1545-7885
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/JulieKlepstad/LiverDevelopment
scopus_import: '1'
status: public
title: Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages
  and postembryonic organ growth dynamics
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 21
year: '2023'
...
---
_id: '14274'
abstract:
- lang: eng
  text: Immune responses rely on the rapid and coordinated migration of leukocytes.
    Whereas it is well established that single-cell migration is often guided by gradients
    of chemokines and other chemoattractants, it remains poorly understood how these
    gradients are generated, maintained, and modulated. By combining experimental
    data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor
    (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor
    that steers migration, CCR7 also acts as a generator and a modulator of chemotactic
    gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively
    internalize the receptor and ligand as part of the canonical GPCR desensitization
    response. We show that CCR7 internalization also acts as an effective sink for
    the chemoattractant, dynamically shaping the spatiotemporal distribution of the
    chemokine. This mechanism drives complex collective migration patterns, enabling
    DCs to create or sharpen chemotactic gradients. We further show that these self-generated
    gradients can sustain the long-range guidance of DCs, adapt collective migration
    patterns to the size and geometry of the environment, and provide a guidance cue
    for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses
    and consumes its ligand can thus provide a novel mode of cellular self-organization.
acknowledgement: "We thank I. de Vries and the Scientific Service Units (Life Sciences,
  Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute
  of Science and Technology Austria for excellent support, as well as all the rotation
  students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis
  work was supported by grants from the European Research Council under the European
  Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant
  agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20)
  to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research
  Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U.
  was supported by the European Union’s Horizon 2020 research and innovation programme
  under the Marie Skłodowska-Curie grant agreement no. 754411."
article_number: adc9584
article_processing_charge: No
article_type: original
author:
- first_name: Jonna H
  full_name: Alanko, Jonna H
  id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
  last_name: Alanko
  orcid: 0000-0002-7698-3061
- first_name: Mehmet C
  full_name: Ucar, Mehmet C
  id: 50B2A802-6007-11E9-A42B-EB23E6697425
  last_name: Ucar
  orcid: 0000-0003-0506-4217
- first_name: Nikola
  full_name: Canigova, Nikola
  id: 3795523E-F248-11E8-B48F-1D18A9856A87
  last_name: Canigova
  orcid: 0000-0002-8518-5926
- first_name: Julian A
  full_name: Stopp, Julian A
  id: 489E3F00-F248-11E8-B48F-1D18A9856A87
  last_name: Stopp
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
citation:
  ama: Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink
    for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>.
    2023;8(87). doi:<a href="https://doi.org/10.1126/sciimmunol.adc9584">10.1126/sciimmunol.adc9584</a>
  apa: Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin,
    J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate
    collective leukocyte migration. <i>Science Immunology</i>. American Association
    for the Advancement of Science. <a href="https://doi.org/10.1126/sciimmunol.adc9584">https://doi.org/10.1126/sciimmunol.adc9584</a>
  chicago: Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz,
    Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor
    and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science
    Immunology</i>. American Association for the Advancement of Science, 2023. <a
    href="https://doi.org/10.1126/sciimmunol.adc9584">https://doi.org/10.1126/sciimmunol.adc9584</a>.
  ieee: J. H. Alanko <i>et al.</i>, “CCR7 acts as both a sensor and a sink for CCL19
    to coordinate collective leukocyte migration,” <i>Science Immunology</i>, vol.
    8, no. 87. American Association for the Advancement of Science, 2023.
  ista: Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB,
    Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective
    leukocyte migration. Science Immunology. 8(87), adc9584.
  mla: Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to
    Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>, vol. 8,
    no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:<a
    href="https://doi.org/10.1126/sciimmunol.adc9584">10.1126/sciimmunol.adc9584</a>.
  short: J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B.
    Hannezo, M.K. Sixt, Science Immunology 8 (2023).
date_created: 2023-09-06T08:07:51Z
date_published: 2023-09-01T00:00:00Z
date_updated: 2023-12-21T14:30:01Z
day: '01'
department:
- _id: MiSi
- _id: EdHa
- _id: NanoFab
doi: 10.1126/sciimmunol.adc9584
ec_funded: 1
external_id:
  isi:
  - '001062110600003'
  pmid:
  - '37656776'
intvolume: '         8'
isi: 1
issue: '87'
keyword:
- General Medicine
- Immunology
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1126/sciimmunol.adc9584
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '724373'
  name: Cellular navigation along spatial gradients
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 265E2996-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01250-B20
  name: Nano-Analytics of Cellular Systems
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Science Immunology
publication_identifier:
  issn:
  - 2470-9468
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
  record:
  - id: '14279'
    relation: research_data
    status: public
  - id: '14697'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte
  migration
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2023'
...
---
_id: '14277'
abstract:
- lang: eng
  text: Living tissues are characterized by an intrinsically mechanochemical interplay
    of active physical forces and complex biochemical signaling pathways. Either feature
    alone can give rise to complex emergent phenomena, for example, mechanically driven
    glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion
    instabilities. An important question is how to quantitatively assess the contribution
    of these different cues to the large-scale dynamics of biological materials. We
    address this in Madin-Darby canine kidney (MDCK) monolayers, considering both
    mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling
    activity and cellular density as well as a mechanically active tissue rheology
    via a self-propelled vertex model. We show that the relative strength of active
    migration forces to mechanochemical couplings controls a transition from a uniform
    active glass to periodic spatiotemporal waves. We parametrize the model from published
    experimental data sets on MDCK monolayers and use it to make new predictions on
    the correlation functions of cellular dynamics and the dynamics of topological
    defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers
    are best described by an intermediary parameter region in which both mechanochemical
    couplings and noisy active propulsion have a strong influence on the dynamics.
    Finally, we study how tissue rheology and ERK waves produce feedback on one another
    and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical
    waves at both the local and global levels.
acknowledgement: We thank all members of the Hannezo group for discussions and suggestions,
  as well as Sound Wai Phow for technical assistance. This work received funding from
  the European Research Council under the EU Horizon 2020 research and innovation
  program Grant Agreement No. 851288 (E.H.), JSPS KAKENHI Grant No. 21H05290, and
  the Ministry of Education under the Research Centres of Excellence program through
  the MBI at NUS.
article_number: '013001'
article_processing_charge: Yes
article_type: original
author:
- first_name: Daniel R
  full_name: Boocock, Daniel R
  id: 453AF628-F248-11E8-B48F-1D18A9856A87
  last_name: Boocock
  orcid: 0000-0002-1585-2631
- first_name: Tsuyoshi
  full_name: Hirashima, Tsuyoshi
  last_name: Hirashima
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Boocock DR, Hirashima T, Hannezo EB. Interplay between mechanochemical patterning
    and glassy dynamics in cellular monolayers. <i>PRX Life</i>. 2023;1(1). doi:<a
    href="https://doi.org/10.1103/prxlife.1.013001">10.1103/prxlife.1.013001</a>
  apa: Boocock, D. R., Hirashima, T., &#38; Hannezo, E. B. (2023). Interplay between
    mechanochemical patterning and glassy dynamics in cellular monolayers. <i>PRX
    Life</i>. American Physical Society. <a href="https://doi.org/10.1103/prxlife.1.013001">https://doi.org/10.1103/prxlife.1.013001</a>
  chicago: Boocock, Daniel R, Tsuyoshi Hirashima, and Edouard B Hannezo. “Interplay
    between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.”
    <i>PRX Life</i>. American Physical Society, 2023. <a href="https://doi.org/10.1103/prxlife.1.013001">https://doi.org/10.1103/prxlife.1.013001</a>.
  ieee: D. R. Boocock, T. Hirashima, and E. B. Hannezo, “Interplay between mechanochemical
    patterning and glassy dynamics in cellular monolayers,” <i>PRX Life</i>, vol.
    1, no. 1. American Physical Society, 2023.
  ista: Boocock DR, Hirashima T, Hannezo EB. 2023. Interplay between mechanochemical
    patterning and glassy dynamics in cellular monolayers. PRX Life. 1(1), 013001.
  mla: Boocock, Daniel R., et al. “Interplay between Mechanochemical Patterning and
    Glassy Dynamics in Cellular Monolayers.” <i>PRX Life</i>, vol. 1, no. 1, 013001,
    American Physical Society, 2023, doi:<a href="https://doi.org/10.1103/prxlife.1.013001">10.1103/prxlife.1.013001</a>.
  short: D.R. Boocock, T. Hirashima, E.B. Hannezo, PRX Life 1 (2023).
date_created: 2023-09-06T08:30:59Z
date_published: 2023-07-20T00:00:00Z
date_updated: 2023-09-15T06:39:17Z
day: '20'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1103/prxlife.1.013001
ec_funded: 1
file:
- access_level: open_access
  checksum: f881d98c89eb9f1aa136d7b781511553
  content_type: application/pdf
  creator: dernst
  date_created: 2023-09-15T06:30:50Z
  date_updated: 2023-09-15T06:30:50Z
  file_id: '14335'
  file_name: 2023_PRXLife_Boocock.pdf
  file_size: 2559520
  relation: main_file
  success: 1
file_date_updated: 2023-09-15T06:30:50Z
has_accepted_license: '1'
intvolume: '         1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: PRX Life
publication_identifier:
  issn:
  - 2835-8279
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
status: public
title: Interplay between mechanochemical patterning and glassy dynamics in cellular
  monolayers
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2023'
...
---
_id: '12162'
abstract:
- lang: eng
  text: Homeostatic balance in the intestinal epithelium relies on a fast cellular
    turnover, which is coordinated by an intricate interplay between biochemical signalling,
    mechanical forces and organ geometry. We review recent modelling approaches that
    have been developed to understand different facets of this remarkable homeostatic
    equilibrium. Existing models offer different, albeit complementary, perspectives
    on the problem. First, biomechanical models aim to explain the local and global
    mechanical stresses driving cell renewal as well as tissue shape maintenance.
    Second, compartmental models provide insights into the conditions necessary to
    keep a constant flow of cells with well-defined ratios of cell types, and how
    perturbations can lead to an unbalance of relative compartment sizes. A third
    family of models address, at the cellular level, the nature and regulation of
    stem fate choices that are necessary to fuel cellular turnover. We also review
    how these different approaches are starting to be integrated together across scales,
    to provide quantitative predictions and new conceptual frameworks to think about
    the dynamics of cell renewal in complex tissues.
acknowledgement: "This work received funding from the ERC under the European Union’s
  Horizon 2020 research and innovation programme (grant agreement No. 851288 to E.H.).\r\nB.
  C-M wants to acknowledge the support of the field of excellence Complexity of Life,
  in Basic Research and Innovation of the University of Graz."
article_processing_charge: Yes (via OA deal)
article_type: review
author:
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  id: 43BE2298-F248-11E8-B48F-1D18A9856A87
  last_name: Corominas-Murtra
  orcid: 0000-0001-9806-5643
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Corominas-Murtra B, Hannezo EB. Modelling the dynamics of mammalian gut homeostasis.
    <i>Seminars in Cell &#38; Developmental Biology</i>. 2023;150-151:58-65. doi:<a
    href="https://doi.org/10.1016/j.semcdb.2022.11.005">10.1016/j.semcdb.2022.11.005</a>
  apa: Corominas-Murtra, B., &#38; Hannezo, E. B. (2023). Modelling the dynamics of
    mammalian gut homeostasis. <i>Seminars in Cell &#38; Developmental Biology</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.semcdb.2022.11.005">https://doi.org/10.1016/j.semcdb.2022.11.005</a>
  chicago: Corominas-Murtra, Bernat, and Edouard B Hannezo. “Modelling the Dynamics
    of Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>.
    Elsevier, 2023. <a href="https://doi.org/10.1016/j.semcdb.2022.11.005">https://doi.org/10.1016/j.semcdb.2022.11.005</a>.
  ieee: B. Corominas-Murtra and E. B. Hannezo, “Modelling the dynamics of mammalian
    gut homeostasis,” <i>Seminars in Cell &#38; Developmental Biology</i>, vol. 150–151.
    Elsevier, pp. 58–65, 2023.
  ista: Corominas-Murtra B, Hannezo EB. 2023. Modelling the dynamics of mammalian
    gut homeostasis. Seminars in Cell &#38; Developmental Biology. 150–151, 58–65.
  mla: Corominas-Murtra, Bernat, and Edouard B. Hannezo. “Modelling the Dynamics of
    Mammalian Gut Homeostasis.” <i>Seminars in Cell &#38; Developmental Biology</i>,
    vol. 150–151, Elsevier, 2023, pp. 58–65, doi:<a href="https://doi.org/10.1016/j.semcdb.2022.11.005">10.1016/j.semcdb.2022.11.005</a>.
  short: B. Corominas-Murtra, E.B. Hannezo, Seminars in Cell &#38; Developmental Biology
    150–151 (2023) 58–65.
date_created: 2023-01-12T12:09:47Z
date_published: 2023-12-02T00:00:00Z
date_updated: 2024-01-16T13:22:32Z
day: '02'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1016/j.semcdb.2022.11.005
ec_funded: 1
external_id:
  isi:
  - '001053522200001'
  pmid:
  - '36470715'
file:
- access_level: open_access
  checksum: c619887cf130f4649bf3035417186004
  content_type: application/pdf
  creator: dernst
  date_created: 2024-01-08T10:16:04Z
  date_updated: 2024-01-08T10:16:04Z
  file_id: '14741'
  file_name: 2023_SeminarsCellDevBiology_CorominasMurtra.pdf
  file_size: 1343750
  relation: main_file
  success: 1
file_date_updated: 2024-01-08T10:16:04Z
has_accepted_license: '1'
isi: 1
keyword:
- Cell Biology
- Developmental Biology
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 58-65
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Seminars in Cell & Developmental Biology
publication_identifier:
  issn:
  - 1084-9521
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modelling the dynamics of mammalian gut homeostasis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 150-151
year: '2023'
...
---
_id: '10825'
abstract:
- lang: eng
  text: In development, lineage segregation is coordinated in time and space. An important
    example is the mammalian inner cell mass, in which the primitive endoderm (PrE,
    founder of the yolk sac) physically segregates from the epiblast (EPI, founder
    of the fetus). While the molecular requirements have been well studied, the physical
    mechanisms determining spatial segregation between EPI and PrE remain elusive.
    Here, we investigate the mechanical basis of EPI and PrE sorting. We find that
    rather than the differences in static cell surface mechanical parameters as in
    classical sorting models, it is the differences in surface fluctuations that robustly
    ensure physical lineage sorting. These differential surface fluctuations systematically
    correlate with differential cellular fluidity, which we propose together constitute
    a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments
    and modeling, we identify cell surface dynamics as a key factor orchestrating
    the correct spatial segregation of the founder embryonic lineages.
acknowledgement: We are grateful to H. Niwa for Dox regulatable PB vector; G. Charras
  for EzrinT567D cDNA; K. Jones for tdTomato ESCs, R26-Confetti ESCs, and laboratory
  assistance; M. Kinoshita for pPB-CAG-H2B-BFP plasmid; P. Humphreys and D. Clements
  for imaging support; G. Chu, P. Attlesey, and staff for animal husbandry; S. Pallett
  for laboratory assistance; C. Mulas for critical feedback on the project; T. Boroviak
  for single-cell RNA-seq; the EMBL Genomics Core Facility for sequencing; and M.
  Merkel for developing and sharing the original version of the 3D Voronoi code. This
  work was financially supported by BBSRC ( BB/Moo4023/1 and BB/T007044/1 to K.J.C.
  and J.N., Alert16 grant BB/R000042 to E.K.P.), Leverhulme Trust ( RPG-2014-080 to
  K.J.C. and J.N.), European Research Council ( 772798 -CellFateTech to K.J.C., 311637
  -MorphoCorDiv and 820188 -NanoMechShape to E.K.P., Starting Grant 851288 to E.H.,
  and 772426 -MeChemGui to K.F.), the Isaac Newton Trust (to E.K.P.), Medical Research
  Council UK (MRC program award MC_UU_00012/5 to E.K.P.), the European Union’s Horizon
  2020 research and innovation program under the Marie Sklodowska-Curie grant agreement
  no. 641639 ( ITN Biopol , H.D.B. and E.K.P.), the Alexander von Humboldt Foundation
  (Alexander von Humboldt Professorship to K.F.), EMBO ALTF 522-2021 (to P.S.), Centre
  for Trophoblast Research (Next Generation fellowship to S.A.), and JSPS Overseas
  Research Fellowships (to A.Y.). The Wellcome-MRC Cambridge Stem Cell Institute receives
  core funding from Wellcome Trust ( 203151/Z/16/Z ) and MRC ( MC_PC_17230 ). For
  the purpose of open access, the author has applied a CC BY public copyright licence
  to any Author Accepted Manuscript version arising from this submission.
article_processing_charge: No
article_type: original
author:
- first_name: Ayaka
  full_name: Yanagida, Ayaka
  last_name: Yanagida
- first_name: Elena
  full_name: Corujo-Simon, Elena
  last_name: Corujo-Simon
- first_name: Christopher K.
  full_name: Revell, Christopher K.
  last_name: Revell
- first_name: Preeti
  full_name: Sahu, Preeti
  id: 55BA52EE-A185-11EA-88FD-18AD3DDC885E
  last_name: Sahu
- first_name: Giuliano G.
  full_name: Stirparo, Giuliano G.
  last_name: Stirparo
- first_name: Irene M.
  full_name: Aspalter, Irene M.
  last_name: Aspalter
- first_name: Alex K.
  full_name: Winkel, Alex K.
  last_name: Winkel
- first_name: Ruby
  full_name: Peters, Ruby
  last_name: Peters
- first_name: Henry
  full_name: De Belly, Henry
  last_name: De Belly
- first_name: Davide A.D.
  full_name: Cassani, Davide A.D.
  last_name: Cassani
- first_name: Sarra
  full_name: Achouri, Sarra
  last_name: Achouri
- first_name: Raphael
  full_name: Blumenfeld, Raphael
  last_name: Blumenfeld
- first_name: Kristian
  full_name: Franze, Kristian
  last_name: Franze
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Ewa K.
  full_name: Paluch, Ewa K.
  last_name: Paluch
- first_name: Jennifer
  full_name: Nichols, Jennifer
  last_name: Nichols
- first_name: Kevin J.
  full_name: Chalut, Kevin J.
  last_name: Chalut
citation:
  ama: Yanagida A, Corujo-Simon E, Revell CK, et al. Cell surface fluctuations regulate
    early embryonic lineage sorting. <i>Cell</i>. 2022;185(5):777-793.e20. doi:<a
    href="https://doi.org/10.1016/j.cell.2022.01.022">10.1016/j.cell.2022.01.022</a>
  apa: Yanagida, A., Corujo-Simon, E., Revell, C. K., Sahu, P., Stirparo, G. G., Aspalter,
    I. M., … Chalut, K. J. (2022). Cell surface fluctuations regulate early embryonic
    lineage sorting. <i>Cell</i>. Cell Press. <a href="https://doi.org/10.1016/j.cell.2022.01.022">https://doi.org/10.1016/j.cell.2022.01.022</a>
  chicago: Yanagida, Ayaka, Elena Corujo-Simon, Christopher K. Revell, Preeti Sahu,
    Giuliano G. Stirparo, Irene M. Aspalter, Alex K. Winkel, et al. “Cell Surface
    Fluctuations Regulate Early Embryonic Lineage Sorting.” <i>Cell</i>. Cell Press,
    2022. <a href="https://doi.org/10.1016/j.cell.2022.01.022">https://doi.org/10.1016/j.cell.2022.01.022</a>.
  ieee: A. Yanagida <i>et al.</i>, “Cell surface fluctuations regulate early embryonic
    lineage sorting,” <i>Cell</i>, vol. 185, no. 5. Cell Press, p. 777–793.e20, 2022.
  ista: Yanagida A, Corujo-Simon E, Revell CK, Sahu P, Stirparo GG, Aspalter IM, Winkel
    AK, Peters R, De Belly H, Cassani DAD, Achouri S, Blumenfeld R, Franze K, Hannezo
    EB, Paluch EK, Nichols J, Chalut KJ. 2022. Cell surface fluctuations regulate
    early embryonic lineage sorting. Cell. 185(5), 777–793.e20.
  mla: Yanagida, Ayaka, et al. “Cell Surface Fluctuations Regulate Early Embryonic
    Lineage Sorting.” <i>Cell</i>, vol. 185, no. 5, Cell Press, 2022, p. 777–793.e20,
    doi:<a href="https://doi.org/10.1016/j.cell.2022.01.022">10.1016/j.cell.2022.01.022</a>.
  short: A. Yanagida, E. Corujo-Simon, C.K. Revell, P. Sahu, G.G. Stirparo, I.M. Aspalter,
    A.K. Winkel, R. Peters, H. De Belly, D.A.D. Cassani, S. Achouri, R. Blumenfeld,
    K. Franze, E.B. Hannezo, E.K. Paluch, J. Nichols, K.J. Chalut, Cell 185 (2022)
    777–793.e20.
date_created: 2022-03-06T23:01:52Z
date_published: 2022-02-22T00:00:00Z
date_updated: 2023-08-02T14:43:50Z
day: '22'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1016/j.cell.2022.01.022
ec_funded: 1
external_id:
  isi:
  - '000796293700007'
  pmid:
  - '35196500'
file:
- access_level: open_access
  checksum: ae305060e8031297771b89dae9e36a29
  content_type: application/pdf
  creator: dernst
  date_created: 2022-03-07T07:55:23Z
  date_updated: 2022-03-07T07:55:23Z
  file_id: '10831'
  file_name: 2022_Cell_Yanagida.pdf
  file_size: 8478995
  relation: main_file
  success: 1
file_date_updated: 2022-03-07T07:55:23Z
has_accepted_license: '1'
intvolume: '       185'
isi: 1
issue: '5'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 777-793.e20
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Cell
publication_identifier:
  eissn:
  - '10974172'
  issn:
  - '00928674'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cell surface fluctuations regulate early embryonic lineage sorting
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 185
year: '2022'
...
---
_id: '12209'
abstract:
- lang: eng
  text: Embryo development requires biochemical signalling to generate patterns of
    cell fates and active mechanical forces to drive tissue shape changes. However,
    how these processes are coordinated, and how tissue patterning is preserved despite
    the cellular flows occurring during morphogenesis, remains poorly understood.
    Gastrulation is a crucial embryonic stage that involves both patterning and internalization
    of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos,
    a gradient in Nodal signalling orchestrates pattern-preserving internalization
    movements by triggering a motility-driven unjamming transition. In addition to
    its role as a morphogen determining embryo patterning, graded Nodal signalling
    mechanically subdivides the mesendoderm into a small fraction of highly protrusive
    leader cells, able to autonomously internalize via local unjamming, and less protrusive
    followers, which need to be pulled inwards by the leaders. The Nodal gradient
    further enforces a code of preferential adhesion coupling leaders to their immediate
    followers, resulting in a collective and ordered mode of internalization that
    preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal
    signalling into minimal active particle simulations quantitatively predicts both
    physiological and experimentally perturbed internalization movements. This provides
    a quantitative framework for how a morphogen-encoded unjamming transition can
    bidirectionally couple tissue mechanics with patterning during complex three-dimensional
    morphogenesis.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the
  manuscript. We also thank the members of the Heisenberg group, in particular A.
  Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging
  and Life Science facilities at IST\r\nAustria for continuous support. We thank C.
  Flandoli for the artwork in the figures. This work was supported by postdoctoral
  fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the
  European Union (European Research Council starting grant 851288 to É.H. and European
  Research Council advanced grant 742573 to C.-P.H.)."
article_processing_charge: No
article_type: original
author:
- first_name: Diana C
  full_name: Nunes Pinheiro, Diana C
  id: 2E839F16-F248-11E8-B48F-1D18A9856A87
  last_name: Nunes Pinheiro
  orcid: 0000-0003-4333-7503
- first_name: Roland
  full_name: Kardos, Roland
  id: 4039350E-F248-11E8-B48F-1D18A9856A87
  last_name: Kardos
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
citation:
  ama: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient
    orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming.
    <i>Nature Physics</i>. 2022;18(12):1482-1493. doi:<a href="https://doi.org/10.1038/s41567-022-01787-6">10.1038/s41567-022-01787-6</a>
  apa: Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., &#38; Heisenberg, C.-P.
    J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis
    via motility-driven unjamming. <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-022-01787-6">https://doi.org/10.1038/s41567-022-01787-6</a>
  chicago: Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp
    J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis
    via Motility-Driven Unjamming.” <i>Nature Physics</i>. Springer Nature, 2022.
    <a href="https://doi.org/10.1038/s41567-022-01787-6">https://doi.org/10.1038/s41567-022-01787-6</a>.
  ieee: D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen
    gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven
    unjamming,” <i>Nature Physics</i>, vol. 18, no. 12. Springer Nature, pp. 1482–1493,
    2022.
  ista: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen
    gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven
    unjamming. Nature Physics. 18(12), 1482–1493.
  mla: Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving
    Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>, vol.
    18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:<a href="https://doi.org/10.1038/s41567-022-01787-6">10.1038/s41567-022-01787-6</a>.
  short: D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature
    Physics 18 (2022) 1482–1493.
date_created: 2023-01-16T09:45:19Z
date_published: 2022-12-01T00:00:00Z
date_updated: 2023-08-04T09:15:58Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
doi: 10.1038/s41567-022-01787-6
ec_funded: 1
external_id:
  isi:
  - '000871319900002'
file:
- access_level: open_access
  checksum: c86a8e8d80d1bfc46d56a01e88a2526a
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-27T07:32:01Z
  date_updated: 2023-01-27T07:32:01Z
  file_id: '12412'
  file_name: 2022_NaturePhysics_Pinheiro.pdf
  file_size: 36703569
  relation: main_file
  success: 1
file_date_updated: 2023-01-27T07:32:01Z
has_accepted_license: '1'
intvolume: '        18'
isi: 1
issue: '12'
keyword:
- General Physics and Astronomy
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 1482-1493
project:
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 850-2017
  name: Coordination of mesendoderm cell fate specification and internalization during
    zebrafish gastrulation
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 850-2017
  name: Coordination of mesendoderm cell fate specification and internalization during
    zebrafish gastrulation
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via
  motility-driven unjamming
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2022'
...
---
_id: '12217'
abstract:
- lang: eng
  text: The development dynamics and self-organization of glandular branched epithelia
    is of utmost importance for our understanding of diverse processes ranging from
    normal tissue growth to the growth of cancerous tissues. Using single primary
    murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix
    and adapted media supplementation, we generate organoids that self-organize into
    highly branched structures displaying a seamless lumen connecting terminal end
    buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis
    phases, each characterized by a unique pattern of cell invasion, matrix deformation,
    protein expression, and respective molecular dependencies. We propose a minimal
    theoretical model of a branching and proliferating tissue, capturing the dynamics
    of the first phases. Observing the interaction of morphogenesis, mechanical environment
    and gene expression in vitro sets a benchmark for the understanding of self-organization
    processes governing complex organoid structure formation processes and branching
    morphogenesis.
acknowledgement: "A.R.B. acknowledges the financial support of the European Research
  Council (ERC) through the funding of the grant Principles of Integrin Mechanics
  and Adhesion (PoINT) and the German Research Foundation (DFG, SFB 1032, project
  ID 201269156). E.H. was supported by the European Union (European Research Council
  Starting Grant 851288). D.S., M.R., and R.R. acknowledge the support by the German
  Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project
  S01, project ID 329628492). C.S. and M.R. acknowledge the support by the German
  Research Foundation (DFG, SFB1321 Modeling and Targeting Pancreatic Cancer, Project
  12, project ID 329628492). M.R. was supported by the German Research Foundation
  (DFG RE 3723/4-1). A.P. and M.R. were supported by the German Cancer Aid (Max-Eder
  Program 111273 and 70114328).\r\nOpen Access funding enabled and organized by Projekt
  DEAL."
article_number: '5219'
article_processing_charge: No
article_type: original
author:
- first_name: S.
  full_name: Randriamanantsoa, S.
  last_name: Randriamanantsoa
- first_name: A.
  full_name: Papargyriou, A.
  last_name: Papargyriou
- first_name: H. C.
  full_name: Maurer, H. C.
  last_name: Maurer
- first_name: K.
  full_name: Peschke, K.
  last_name: Peschke
- first_name: M.
  full_name: Schuster, M.
  last_name: Schuster
- first_name: G.
  full_name: Zecchin, G.
  last_name: Zecchin
- first_name: K.
  full_name: Steiger, K.
  last_name: Steiger
- first_name: R.
  full_name: Öllinger, R.
  last_name: Öllinger
- first_name: D.
  full_name: Saur, D.
  last_name: Saur
- first_name: C.
  full_name: Scheel, C.
  last_name: Scheel
- first_name: R.
  full_name: Rad, R.
  last_name: Rad
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: M.
  full_name: Reichert, M.
  last_name: Reichert
- first_name: A. R.
  full_name: Bausch, A. R.
  last_name: Bausch
citation:
  ama: Randriamanantsoa S, Papargyriou A, Maurer HC, et al. Spatiotemporal dynamics
    of self-organized branching in pancreas-derived organoids. <i>Nature Communications</i>.
    2022;13. doi:<a href="https://doi.org/10.1038/s41467-022-32806-y">10.1038/s41467-022-32806-y</a>
  apa: Randriamanantsoa, S., Papargyriou, A., Maurer, H. C., Peschke, K., Schuster,
    M., Zecchin, G., … Bausch, A. R. (2022). Spatiotemporal dynamics of self-organized
    branching in pancreas-derived organoids. <i>Nature Communications</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s41467-022-32806-y">https://doi.org/10.1038/s41467-022-32806-y</a>
  chicago: Randriamanantsoa, S., A. Papargyriou, H. C. Maurer, K. Peschke, M. Schuster,
    G. Zecchin, K. Steiger, et al. “Spatiotemporal Dynamics of Self-Organized Branching
    in Pancreas-Derived Organoids.” <i>Nature Communications</i>. Springer Nature,
    2022. <a href="https://doi.org/10.1038/s41467-022-32806-y">https://doi.org/10.1038/s41467-022-32806-y</a>.
  ieee: S. Randriamanantsoa <i>et al.</i>, “Spatiotemporal dynamics of self-organized
    branching in pancreas-derived organoids,” <i>Nature Communications</i>, vol. 13.
    Springer Nature, 2022.
  ista: Randriamanantsoa S, Papargyriou A, Maurer HC, Peschke K, Schuster M, Zecchin
    G, Steiger K, Öllinger R, Saur D, Scheel C, Rad R, Hannezo EB, Reichert M, Bausch
    AR. 2022. Spatiotemporal dynamics of self-organized branching in pancreas-derived
    organoids. Nature Communications. 13, 5219.
  mla: Randriamanantsoa, S., et al. “Spatiotemporal Dynamics of Self-Organized Branching
    in Pancreas-Derived Organoids.” <i>Nature Communications</i>, vol. 13, 5219, Springer
    Nature, 2022, doi:<a href="https://doi.org/10.1038/s41467-022-32806-y">10.1038/s41467-022-32806-y</a>.
  short: S. Randriamanantsoa, A. Papargyriou, H.C. Maurer, K. Peschke, M. Schuster,
    G. Zecchin, K. Steiger, R. Öllinger, D. Saur, C. Scheel, R. Rad, E.B. Hannezo,
    M. Reichert, A.R. Bausch, Nature Communications 13 (2022).
date_created: 2023-01-16T09:46:53Z
date_published: 2022-09-05T00:00:00Z
date_updated: 2023-08-04T09:25:23Z
day: '05'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1038/s41467-022-32806-y
ec_funded: 1
external_id:
  isi:
  - '000850348400025'
file:
- access_level: open_access
  checksum: 295261b5172274fd5b8f85a6a6058828
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-27T08:14:48Z
  date_updated: 2023-01-27T08:14:48Z
  file_id: '12416'
  file_name: 2022_NatureCommunications_Randriamanantsoa.pdf
  file_size: 22645149
  relation: main_file
  success: 1
file_date_updated: 2023-01-27T08:14:48Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
keyword:
- General Physics and Astronomy
- General Biochemistry
- Genetics and Molecular Biology
- General Chemistry
- Multidisciplinary
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '13068'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '12253'
abstract:
- lang: eng
  text: The sculpting of germ layers during gastrulation relies on the coordinated
    migration of progenitor cells, yet the cues controlling these long-range directed
    movements remain largely unknown. While directional migration often relies on
    a chemokine gradient generated from a localized source, we find that zebrafish
    ventrolateral mesoderm is guided by a self-generated gradient of the initially
    uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the
    Apelin receptor, which is specifically expressed in mesodermal cells, has a dual
    role during gastrulation, acting as a scavenger receptor to generate a Toddler
    gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover
    a single receptor–based self-generated gradient as the enigmatic guidance cue
    that can robustly steer the directional migration of mesoderm through the complex
    and continuously changing environment of the gastrulating embryo.
acknowledgement: 'We thank K. Aumayer and the team of the biooptics facility at the
  Vienna Biocenter, particularly P. Pasierbek and T. Müller, for support with microscopy;
  K. Panser, C. Pribitzer, and the animal facility personnel for taking care of zebrafish;
  M. Binner and A. Bandura for help with genotyping; M. Codina Tobias for help with
  establishing the conditions for the Toddler overexpression compensation experiment;
  T. Lubiana Alves for sharing the code for scRNA-Seq analyses; the Heisenberg laboratory,
  particularly D. Pinheiro, for joint laboratory meetings, discussions on the project,
  and providing the tg(gsc:CAAX-GFP) fish line; the Raz laboratory for providing the
  Lifeact-GFP plasmid; A. Andersen, A. Schier, C.-P. Heisenberg, and E. Tanaka for
  comments on the manuscript; and the entire Pauli laboratory, particularly K. Gert
  and V. Deneke, for valuable discussions and feedback on the manuscript. Funding:
  Work in A.P.’s laboratory has been supported by the IMP, which receives institutional
  funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter
  grant FFG-852936), as well as the FWF START program (Y 1031-B28 to A.P.), the Human
  Frontier Science Program (HFSP) Career Development Award (CDA00066/2015 to A.P.)
  and Young Investigator Grant (RGY0079/2020 to A.P.), the SFB RNA-Deco (project number
  F 80 to A.P.), a Whitman Center Fellowship from the Marine Biological Laboratory
  (to A.P.), and EMBO-YIP funds (to A.P.). This work was supported by the European
  Union (European Research Council Starting Grant 851288 to E.H.). For the purpose
  of Open Access, the authors have applied a CC BY public copyright license to any
  Author Accepted Manuscript (AAM) version arising from this submission.'
article_number: eadd2488
article_processing_charge: No
article_type: original
author:
- first_name: Jessica
  full_name: Stock, Jessica
  last_name: Stock
- first_name: Tomas
  full_name: Kazmar, Tomas
  last_name: Kazmar
- first_name: Friederike
  full_name: Schlumm, Friederike
  last_name: Schlumm
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Andrea
  full_name: Pauli, Andrea
  last_name: Pauli
citation:
  ama: Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. A self-generated Toddler
    gradient guides mesodermal cell migration. <i>Science Advances</i>. 2022;8(37).
    doi:<a href="https://doi.org/10.1126/sciadv.add2488">10.1126/sciadv.add2488</a>
  apa: Stock, J., Kazmar, T., Schlumm, F., Hannezo, E. B., &#38; Pauli, A. (2022).
    A self-generated Toddler gradient guides mesodermal cell migration. <i>Science
    Advances</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.add2488">https://doi.org/10.1126/sciadv.add2488</a>
  chicago: Stock, Jessica, Tomas Kazmar, Friederike Schlumm, Edouard B Hannezo, and
    Andrea Pauli. “A Self-Generated Toddler Gradient Guides Mesodermal Cell Migration.”
    <i>Science Advances</i>. American Association for the Advancement of Science,
    2022. <a href="https://doi.org/10.1126/sciadv.add2488">https://doi.org/10.1126/sciadv.add2488</a>.
  ieee: J. Stock, T. Kazmar, F. Schlumm, E. B. Hannezo, and A. Pauli, “A self-generated
    Toddler gradient guides mesodermal cell migration,” <i>Science Advances</i>, vol.
    8, no. 37. American Association for the Advancement of Science, 2022.
  ista: Stock J, Kazmar T, Schlumm F, Hannezo EB, Pauli A. 2022. A self-generated
    Toddler gradient guides mesodermal cell migration. Science Advances. 8(37), eadd2488.
  mla: Stock, Jessica, et al. “A Self-Generated Toddler Gradient Guides Mesodermal
    Cell Migration.” <i>Science Advances</i>, vol. 8, no. 37, eadd2488, American Association
    for the Advancement of Science, 2022, doi:<a href="https://doi.org/10.1126/sciadv.add2488">10.1126/sciadv.add2488</a>.
  short: J. Stock, T. Kazmar, F. Schlumm, E.B. Hannezo, A. Pauli, Science Advances
    8 (2022).
date_created: 2023-01-16T09:57:10Z
date_published: 2022-09-14T00:00:00Z
date_updated: 2023-08-04T09:49:59Z
day: '14'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1126/sciadv.add2488
ec_funded: 1
external_id:
  isi:
  - '000888875000009'
  pmid:
  - '36103529'
file:
- access_level: open_access
  checksum: f59cdb824e5d4221045def81f46f6c65
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T09:27:49Z
  date_updated: 2023-01-30T09:27:49Z
  file_id: '12444'
  file_name: 2022_ScienceAdvances_Stock.pdf
  file_size: 1636732
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T09:27:49Z
has_accepted_license: '1'
intvolume: '         8'
isi: 1
issue: '37'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Science Advances
publication_identifier:
  issn:
  - 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: A self-generated Toddler gradient guides mesodermal cell migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 8
year: '2022'
...
---
_id: '12274'
abstract:
- lang: eng
  text: The morphology and functionality of the epithelial lining differ along the
    intestinal tract, but tissue renewal at all sites is driven by stem cells at the
    base of crypts1,2,3. Whether stem cell numbers and behaviour vary at different
    sites is unknown. Here we show using intravital microscopy that, despite similarities
    in the number and distribution of proliferative cells with an Lgr5 signature in
    mice, small intestinal crypts contain twice as many effective stem cells as large
    intestinal crypts. We find that, although passively displaced by a conveyor-belt-like
    upward movement, small intestinal cells positioned away from the crypt base can
    function as long-term effective stem cells owing to Wnt-dependent retrograde cellular
    movement. By contrast, the near absence of retrograde movement in the large intestine
    restricts cell repositioning, leading to a reduction in effective stem cell number.
    Moreover, after suppression of the retrograde movement in the small intestine,
    the number of effective stem cells is reduced, and the rate of monoclonal conversion
    of crypts is accelerated. Together, these results show that the number of effective
    stem cells is determined by active retrograde movement, revealing a new channel
    of stem cell regulation that can be experimentally and pharmacologically manipulated.
acknowledgement: We thank the members of the van Rheenen laboratory for reading the
  manuscript, and the members of the bioimaging, FACS and animal facility of the NKI
  for experimental support. We acknowledge the staff at the MedH Flow Cytometry core
  facility, Karolinska Institutet, and LCI facility/Nikon Center of Excellence, Karolinska
  Institutet. This work was financially supported by the Netherlands Organization
  of Scientific Research NWO (Veni grant 863.15.011 to S.I.J.E. and Vici grant 09150182110004
  to J.v.R.) and the CancerGenomics.nl (Netherlands Organisation for Scientific Research)
  program (to J.v.R.) the Doctor Josef Steiner Foundation (to J.v.R). B.D.S. acknowledges
  funding from the Royal Society E.P. Abraham Research Professorship (RP\R1\180165)
  and the Wellcome Trust (098357/Z/12/Z and 219478/Z/19/Z). B.C.-M. acknowledges the
  support of the field of excellence ‘Complexity of life in basic research and innovation’
  of the University of Graz. O.J.S. and their laboratory acknowledge CRUK core funding
  to the CRUK Beatson Institute (A17196 and A31287) and CRUK core funding to the Sansom
  laboratory (A21139). P.K. and their laboratory are supported by grants from the
  Swedish Research Council (2018-03078), Cancerfonden (190634), Academy of Finland
  Centre of Excellence (266869, 304591 and 320185) and the Jane and Aatos Erkko Foundation.
  P.L. has received funding from the European Research Council (ERC) under the European
  Union’s Horizon 2020 research and innovation programme (grant agreement no. 758617).
  E.H. acknowledges funding from the European Research Council (ERC) under the European
  Union’s Horizon 2020 research and innovation programme (grant agreement no. 851288).
article_processing_charge: No
article_type: original
author:
- first_name: Maria
  full_name: Azkanaz, Maria
  last_name: Azkanaz
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  id: 43BE2298-F248-11E8-B48F-1D18A9856A87
  last_name: Corominas-Murtra
  orcid: 0000-0001-9806-5643
- first_name: Saskia I. J.
  full_name: Ellenbroek, Saskia I. J.
  last_name: Ellenbroek
- first_name: Lotte
  full_name: Bruens, Lotte
  last_name: Bruens
- first_name: Anna T.
  full_name: Webb, Anna T.
  last_name: Webb
- first_name: Dimitrios
  full_name: Laskaris, Dimitrios
  last_name: Laskaris
- first_name: Koen C.
  full_name: Oost, Koen C.
  last_name: Oost
- first_name: Simona J. A.
  full_name: Lafirenze, Simona J. A.
  last_name: Lafirenze
- first_name: Karl
  full_name: Annusver, Karl
  last_name: Annusver
- first_name: Hendrik A.
  full_name: Messal, Hendrik A.
  last_name: Messal
- first_name: Sharif
  full_name: Iqbal, Sharif
  last_name: Iqbal
- first_name: Dustin J.
  full_name: Flanagan, Dustin J.
  last_name: Flanagan
- first_name: David J.
  full_name: Huels, David J.
  last_name: Huels
- first_name: Felipe
  full_name: Rojas-Rodríguez, Felipe
  last_name: Rojas-Rodríguez
- first_name: Miguel
  full_name: Vizoso, Miguel
  last_name: Vizoso
- first_name: Maria
  full_name: Kasper, Maria
  last_name: Kasper
- first_name: Owen J.
  full_name: Sansom, Owen J.
  last_name: Sansom
- first_name: Hugo J.
  full_name: Snippert, Hugo J.
  last_name: Snippert
- first_name: Prisca
  full_name: Liberali, Prisca
  last_name: Liberali
- first_name: Benjamin D.
  full_name: Simons, Benjamin D.
  last_name: Simons
- first_name: Pekka
  full_name: Katajisto, Pekka
  last_name: Katajisto
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Jacco
  full_name: van Rheenen, Jacco
  last_name: van Rheenen
citation:
  ama: Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, et al. Retrograde movements
    determine effective stem cell numbers in the intestine. <i>Nature</i>. 2022;607(7919):548-554.
    doi:<a href="https://doi.org/10.1038/s41586-022-04962-0">10.1038/s41586-022-04962-0</a>
  apa: Azkanaz, M., Corominas-Murtra, B., Ellenbroek, S. I. J., Bruens, L., Webb,
    A. T., Laskaris, D., … van Rheenen, J. (2022). Retrograde movements determine
    effective stem cell numbers in the intestine. <i>Nature</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41586-022-04962-0">https://doi.org/10.1038/s41586-022-04962-0</a>
  chicago: Azkanaz, Maria, Bernat Corominas-Murtra, Saskia I. J. Ellenbroek, Lotte
    Bruens, Anna T. Webb, Dimitrios Laskaris, Koen C. Oost, et al. “Retrograde Movements
    Determine Effective Stem Cell Numbers in the Intestine.” <i>Nature</i>. Springer
    Nature, 2022. <a href="https://doi.org/10.1038/s41586-022-04962-0">https://doi.org/10.1038/s41586-022-04962-0</a>.
  ieee: M. Azkanaz <i>et al.</i>, “Retrograde movements determine effective stem cell
    numbers in the intestine,” <i>Nature</i>, vol. 607, no. 7919. Springer Nature,
    pp. 548–554, 2022.
  ista: Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris
    D, Oost KC, Lafirenze SJA, Annusver K, Messal HA, Iqbal S, Flanagan DJ, Huels
    DJ, Rojas-Rodríguez F, Vizoso M, Kasper M, Sansom OJ, Snippert HJ, Liberali P,
    Simons BD, Katajisto P, Hannezo EB, van Rheenen J. 2022. Retrograde movements
    determine effective stem cell numbers in the intestine. Nature. 607(7919), 548–554.
  mla: Azkanaz, Maria, et al. “Retrograde Movements Determine Effective Stem Cell
    Numbers in the Intestine.” <i>Nature</i>, vol. 607, no. 7919, Springer Nature,
    2022, pp. 548–54, doi:<a href="https://doi.org/10.1038/s41586-022-04962-0">10.1038/s41586-022-04962-0</a>.
  short: M. Azkanaz, B. Corominas-Murtra, S.I.J. Ellenbroek, L. Bruens, A.T. Webb,
    D. Laskaris, K.C. Oost, S.J.A. Lafirenze, K. Annusver, H.A. Messal, S. Iqbal,
    D.J. Flanagan, D.J. Huels, F. Rojas-Rodríguez, M. Vizoso, M. Kasper, O.J. Sansom,
    H.J. Snippert, P. Liberali, B.D. Simons, P. Katajisto, E.B. Hannezo, J. van Rheenen,
    Nature 607 (2022) 548–554.
date_created: 2023-01-16T10:01:29Z
date_published: 2022-07-13T00:00:00Z
date_updated: 2023-10-03T11:16:30Z
day: '13'
department:
- _id: EdHa
doi: 10.1038/s41586-022-04962-0
ec_funded: 1
external_id:
  isi:
  - '000824430000004'
  pmid:
  - '35831497'
intvolume: '       607'
isi: 1
issue: '7919'
keyword:
- Multidisciplinary
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://helda.helsinki.fi/items/94433455-4854-45c0-9de8-7326caea8780
month: '07'
oa: 1
oa_version: Submitted Version
page: 548-554
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/JaccovanRheenenLab/Retrograde_movement_Azkanaz_Nature_2022
scopus_import: '1'
status: public
title: Retrograde movements determine effective stem cell numbers in the intestine
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 607
year: '2022'
...
---
_id: '8602'
abstract:
- lang: eng
  text: Collective cell migration offers a rich field of study for non-equilibrium
    physics and cellular biology, revealing phenomena such as glassy dynamics, pattern
    formation and active turbulence. However, how mechanical and chemical signalling
    are integrated at the cellular level to give rise to such collective behaviours
    remains unclear. We address this by focusing on the highly conserved phenomenon
    of spatiotemporal waves of density and extracellular signal-regulated kinase (ERK)
    activation, which appear both in vitro and in vivo during collective cell migration
    and wound healing. First, we propose a biophysical theory, backed by mechanical
    and optogenetic perturbation experiments, showing that patterns can be quantitatively
    explained by a mechanochemical coupling between active cellular tensions and the
    mechanosensitive ERK pathway. Next, we demonstrate how this biophysical mechanism
    can robustly induce long-ranged order and migration in a desired orientation,
    and we determine the theoretically optimal wavelength and period for inducing
    maximal migration towards free edges, which fits well with experimentally observed
    dynamics. We thereby provide a bridge between the biophysical origin of spatiotemporal
    instabilities and the design principles of robust and efficient long-ranged migration.
acknowledgement: We would like to thank G. Tkacik and all of the members of the Hannezo
  and Hirashima groups for useful discussions, X. Trepat for help on traction force
  microscopy and M. Matsuda for use of the lab facility. E.H. acknowledges grants
  from the Austrian Science Fund (FWF) (P 31639) and the European Research Council
  (851288). T.H. acknowledges a grant from JST, PRESTO (JPMJPR1949). This project
  has received funding from the European Union’s Horizon 2020 research and innovation
  programme under the Marie Skłodowska-Curie grant agreement no. 665385 (to D.B.),
  from JSPS KAKENHI grant no. 17J02107 (to N.H.) and from the SPIRITS 2018 of Kyoto
  University (to E.H. and T.H.).
article_processing_charge: No
article_type: original
author:
- first_name: Daniel R
  full_name: Boocock, Daniel R
  id: 453AF628-F248-11E8-B48F-1D18A9856A87
  last_name: Boocock
  orcid: 0000-0002-1585-2631
- first_name: Naoya
  full_name: Hino, Naoya
  last_name: Hino
- first_name: Natalia
  full_name: Ruzickova, Natalia
  id: D2761128-D73D-11E9-A1BF-BA0DE6697425
  last_name: Ruzickova
- first_name: Tsuyoshi
  full_name: Hirashima, Tsuyoshi
  last_name: Hirashima
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. Theory of mechanochemical
    patterning and optimal migration in cell monolayers. <i>Nature Physics</i>. 2021;17:267-274.
    doi:<a href="https://doi.org/10.1038/s41567-020-01037-7">10.1038/s41567-020-01037-7</a>
  apa: Boocock, D. R., Hino, N., Ruzickova, N., Hirashima, T., &#38; Hannezo, E. B.
    (2021). Theory of mechanochemical patterning and optimal migration in cell monolayers.
    <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-020-01037-7">https://doi.org/10.1038/s41567-020-01037-7</a>
  chicago: Boocock, Daniel R, Naoya Hino, Natalia Ruzickova, Tsuyoshi Hirashima, and
    Edouard B Hannezo. “Theory of Mechanochemical Patterning and Optimal Migration
    in Cell Monolayers.” <i>Nature Physics</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41567-020-01037-7">https://doi.org/10.1038/s41567-020-01037-7</a>.
  ieee: D. R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, and E. B. Hannezo, “Theory
    of mechanochemical patterning and optimal migration in cell monolayers,” <i>Nature
    Physics</i>, vol. 17. Springer Nature, pp. 267–274, 2021.
  ista: Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. 2021. Theory of
    mechanochemical patterning and optimal migration in cell monolayers. Nature Physics.
    17, 267–274.
  mla: Boocock, Daniel R., et al. “Theory of Mechanochemical Patterning and Optimal
    Migration in Cell Monolayers.” <i>Nature Physics</i>, vol. 17, Springer Nature,
    2021, pp. 267–74, doi:<a href="https://doi.org/10.1038/s41567-020-01037-7">10.1038/s41567-020-01037-7</a>.
  short: D.R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, E.B. Hannezo, Nature Physics
    17 (2021) 267–274.
date_created: 2020-10-04T22:01:37Z
date_published: 2021-02-01T00:00:00Z
date_updated: 2023-08-04T11:02:41Z
day: '01'
department:
- _id: EdHa
doi: 10.1038/s41567-020-01037-7
ec_funded: 1
external_id:
  isi:
  - '000573519500002'
intvolume: '        17'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2020.05.15.096479
month: '02'
oa: 1
oa_version: Preprint
page: 267-274
project:
- _id: 268294B6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31639
  name: Active mechano-chemical description of the cell cytoskeleton
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: Nature Physics
publication_identifier:
  eissn:
  - '17452481'
  issn:
  - '17452473'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/wound-healing-waves/
  record:
  - id: '12964'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Theory of mechanochemical patterning and optimal migration in cell monolayers
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 17
year: '2021'
...
---
_id: '9244'
abstract:
- lang: eng
  text: 'Organ function depends on tissues adopting the correct architecture. However,
    insights into organ architecture are currently hampered by an absence of standardized
    quantitative 3D analysis. We aimed to develop a robust technology to visualize,
    digitalize, and segment the architecture of two tubular systems in 3D: double
    resin casting micro computed tomography (DUCT). As proof of principle, we applied
    DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized
    by intrahepatic bile duct paucity, that can spontaneously generate a biliary system
    in adulthood. DUCT identified increased central biliary branching and peripheral
    bile duct tortuosity as two compensatory processes occurring in distinct regions
    of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume
    and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis,
    which can reveal novel phenotypes and provide a standardized method of defining
    liver architecture in mouse models.'
acknowledgement: "Work in ERA lab is supported by the Swedish Research Council, the
  Center of Innovative Medicine (CIMED) Grant, Karolinska Institutet, and the Heart
  and Lung Foundation, and\r\nthe Daniel Alagille Award from the European Association
  for the Study of the Liver. One project in ERA lab is funded by ModeRNA, unrelated
  to this project. The funders have no role in the design or interpretation of the
  work. SH has been supported by a KI-MU PhD student program, and by a Wera Ekstro¨m
  Foundation Scholarship. We are grateful for support from Tornspiran foundation to
  NVH. JK: This research was carried out under the project CEITEC 2020 (LQ1601) with
  financial support from the Ministry of Education, Youth and Sports of the Czech
  Republic under the National Sustainability Programme II and CzechNanoLab Research
  Infrastructure supported by MEYS CR (LM2018110) . UL: The financial support from
  the Swedish Research Council and ICMC (Integrated CardioMetabolic Center) is acknowledged.
  JJ: The work was supported by the Grant Agency of Masaryk University (project no.
  MUNI/A/1565/2018). We thank Kari Huppert and Stacey Huppert for their expertise
  and help regarding bile duct cannulation and their laboratory hospitality. We also
  thank Nadja Schultz and Charlotte L Mattsson for their help with common bile duct
  cannulation. We thank Daniel Holl for his help with trachea cannulation. We thank
  Nikos Papadogiannakis for his assistance with mild Alagille biopsy samples and discussion.
  We thank Karolinska Biomedicum Imaging Core, especially Shigeaki Kanatani for his
  help with image analysis. We thank Jan Masek and Carolina Gutierrez for their scientific
  input in manuscript writing. We thank Peter Ranefall and the BioImage Informatics
  (SciLife national facility) for their help writing parts of the MATLAB pipeline.\r\nThe
  TROMA-III antibody developed by Rolf Kemler was obtained from the Developmental
  Studies Hybridoma (DSHB) Bank developed under the auspices of NICHD and maintained
  by The University of Iowa, Department of Biological Sciences, Iowa City, IA52242.
  We thank Goncalo M Brito for all illustrations. This work was supported by the European
  Union (European Research Council Starting grant 851288 to E.H.)."
article_number: e60916
article_processing_charge: No
article_type: original
author:
- first_name: Simona
  full_name: Hankeova, Simona
  last_name: Hankeova
- first_name: Jakub
  full_name: Salplachta, Jakub
  last_name: Salplachta
- first_name: Tomas
  full_name: Zikmund, Tomas
  last_name: Zikmund
- first_name: Michaela
  full_name: Kavkova, Michaela
  last_name: Kavkova
- first_name: Noémi
  full_name: Van Hul, Noémi
  last_name: Van Hul
- first_name: Adam
  full_name: Brinek, Adam
  last_name: Brinek
- first_name: Veronika
  full_name: Smekalova, Veronika
  last_name: Smekalova
- first_name: Jakub
  full_name: Laznovsky, Jakub
  last_name: Laznovsky
- first_name: Feven
  full_name: Dawit, Feven
  last_name: Dawit
- first_name: Josef
  full_name: Jaros, Josef
  last_name: Jaros
- first_name: Vítězslav
  full_name: Bryja, Vítězslav
  last_name: Bryja
- first_name: Urban
  full_name: Lendahl, Urban
  last_name: Lendahl
- first_name: Ewa
  full_name: Ellis, Ewa
  last_name: Ellis
- first_name: Antal
  full_name: Nemeth, Antal
  last_name: Nemeth
- first_name: Björn
  full_name: Fischler, Björn
  last_name: Fischler
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Jozef
  full_name: Kaiser, Jozef
  last_name: Kaiser
- first_name: Emma Rachel
  full_name: Andersson, Emma Rachel
  last_name: Andersson
citation:
  ama: Hankeova S, Salplachta J, Zikmund T, et al. DUCT reveals architectural mechanisms
    contributing to bile duct recovery in a mouse model for alagille syndrome. <i>eLife</i>.
    2021;10. doi:<a href="https://doi.org/10.7554/eLife.60916">10.7554/eLife.60916</a>
  apa: Hankeova, S., Salplachta, J., Zikmund, T., Kavkova, M., Van Hul, N., Brinek,
    A., … Andersson, E. R. (2021). DUCT reveals architectural mechanisms contributing
    to bile duct recovery in a mouse model for alagille syndrome. <i>ELife</i>. eLife
    Sciences Publications. <a href="https://doi.org/10.7554/eLife.60916">https://doi.org/10.7554/eLife.60916</a>
  chicago: Hankeova, Simona, Jakub Salplachta, Tomas Zikmund, Michaela Kavkova, Noémi
    Van Hul, Adam Brinek, Veronika Smekalova, et al. “DUCT Reveals Architectural Mechanisms
    Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” <i>ELife</i>.
    eLife Sciences Publications, 2021. <a href="https://doi.org/10.7554/eLife.60916">https://doi.org/10.7554/eLife.60916</a>.
  ieee: S. Hankeova <i>et al.</i>, “DUCT reveals architectural mechanisms contributing
    to bile duct recovery in a mouse model for alagille syndrome,” <i>eLife</i>, vol.
    10. eLife Sciences Publications, 2021.
  ista: Hankeova S, Salplachta J, Zikmund T, Kavkova M, Van Hul N, Brinek A, Smekalova
    V, Laznovsky J, Dawit F, Jaros J, Bryja V, Lendahl U, Ellis E, Nemeth A, Fischler
    B, Hannezo EB, Kaiser J, Andersson ER. 2021. DUCT reveals architectural mechanisms
    contributing to bile duct recovery in a mouse model for alagille syndrome. eLife.
    10, e60916.
  mla: Hankeova, Simona, et al. “DUCT Reveals Architectural Mechanisms Contributing
    to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” <i>ELife</i>, vol.
    10, e60916, eLife Sciences Publications, 2021, doi:<a href="https://doi.org/10.7554/eLife.60916">10.7554/eLife.60916</a>.
  short: S. Hankeova, J. Salplachta, T. Zikmund, M. Kavkova, N. Van Hul, A. Brinek,
    V. Smekalova, J. Laznovsky, F. Dawit, J. Jaros, V. Bryja, U. Lendahl, E. Ellis,
    A. Nemeth, B. Fischler, E.B. Hannezo, J. Kaiser, E.R. Andersson, ELife 10 (2021).
date_created: 2021-03-14T23:01:34Z
date_published: 2021-02-26T00:00:00Z
date_updated: 2023-08-07T14:12:54Z
day: '26'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.7554/eLife.60916
ec_funded: 1
external_id:
  isi:
  - '000625357100001'
  pmid:
  - '33635272'
file:
- access_level: open_access
  checksum: 20ccf4dfe46c48cf986794c8bf4fd1cb
  content_type: application/pdf
  creator: dernst
  date_created: 2021-03-22T08:50:33Z
  date_updated: 2021-03-22T08:50:33Z
  file_id: '9271'
  file_name: 2021_eLife_Hankeova.pdf
  file_size: 9259690
  relation: main_file
  success: 1
file_date_updated: 2021-03-22T08:50:33Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: eLife
publication_identifier:
  eissn:
  - 2050084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: DUCT reveals architectural mechanisms contributing to bile duct recovery in
  a mouse model for alagille syndrome
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...
---
_id: '9316'
abstract:
- lang: eng
  text: Embryo morphogenesis is impacted by dynamic changes in tissue material properties,
    which have been proposed to occur via processes akin to phase transitions (PTs).
    Here, we show that rigidity percolation provides a simple and robust theoretical
    framework to predict material/structural PTs of embryonic tissues from local cell
    connectivity. By using percolation theory, combined with directly monitoring dynamic
    changes in tissue rheology and cell contact mechanics, we demonstrate that the
    zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small
    reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively
    predict and experimentally verify hallmarks of PTs, including power-law exponents
    and associated discontinuities of macroscopic observables. Finally, we show that
    this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions
    causing random and, consequently, uniform changes in cell connectivity. Collectively,
    our theoretical and experimental findings reveal the structural basis of material
    PTs in an organismal context.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank Carl Goodrich and the members of the Heisenberg and Hannezo
  groups, in particular Reka Korei, for help, technical advice, and discussions; and
  the Bioimaging and zebrafish facilities of the IST Austria for continuous support.
  This work was supported by the Elise Richter Program of Austrian Science Fund (FWF)
  to N.I.P. ( V 736-B26 ) and the European Union (European Research Council Advanced
  Grant 742573 to C.-P.H. and European Research Council Starting Grant 851288 to E.H.).
article_processing_charge: No
article_type: original
author:
- first_name: Nicoletta
  full_name: Petridou, Nicoletta
  id: 2A003F6C-F248-11E8-B48F-1D18A9856A87
  last_name: Petridou
  orcid: 0000-0002-8451-1195
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  id: 43BE2298-F248-11E8-B48F-1D18A9856A87
  last_name: Corominas-Murtra
  orcid: 0000-0001-9806-5643
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Petridou N, Corominas-Murtra B, Heisenberg C-PJ, Hannezo EB. Rigidity percolation
    uncovers a structural basis for embryonic tissue phase transitions. <i>Cell</i>.
    2021;184(7):1914-1928.e19. doi:<a href="https://doi.org/10.1016/j.cell.2021.02.017">10.1016/j.cell.2021.02.017</a>
  apa: Petridou, N., Corominas-Murtra, B., Heisenberg, C.-P. J., &#38; Hannezo, E.
    B. (2021). Rigidity percolation uncovers a structural basis for embryonic tissue
    phase transitions. <i>Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.cell.2021.02.017">https://doi.org/10.1016/j.cell.2021.02.017</a>
  chicago: Petridou, Nicoletta, Bernat Corominas-Murtra, Carl-Philipp J Heisenberg,
    and Edouard B Hannezo. “Rigidity Percolation Uncovers a Structural Basis for Embryonic
    Tissue Phase Transitions.” <i>Cell</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.cell.2021.02.017">https://doi.org/10.1016/j.cell.2021.02.017</a>.
  ieee: N. Petridou, B. Corominas-Murtra, C.-P. J. Heisenberg, and E. B. Hannezo,
    “Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions,”
    <i>Cell</i>, vol. 184, no. 7. Elsevier, p. 1914–1928.e19, 2021.
  ista: Petridou N, Corominas-Murtra B, Heisenberg C-PJ, Hannezo EB. 2021. Rigidity
    percolation uncovers a structural basis for embryonic tissue phase transitions.
    Cell. 184(7), 1914–1928.e19.
  mla: Petridou, Nicoletta, et al. “Rigidity Percolation Uncovers a Structural Basis
    for Embryonic Tissue Phase Transitions.” <i>Cell</i>, vol. 184, no. 7, Elsevier,
    2021, p. 1914–1928.e19, doi:<a href="https://doi.org/10.1016/j.cell.2021.02.017">10.1016/j.cell.2021.02.017</a>.
  short: N. Petridou, B. Corominas-Murtra, C.-P.J. Heisenberg, E.B. Hannezo, Cell
    184 (2021) 1914–1928.e19.
date_created: 2021-04-11T22:01:14Z
date_published: 2021-04-01T00:00:00Z
date_updated: 2023-08-07T14:33:59Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
doi: 10.1016/j.cell.2021.02.017
ec_funded: 1
external_id:
  isi:
  - '000636734000022'
  pmid:
  - '33730596'
file:
- access_level: open_access
  checksum: 1e5295fbd9c2a459173ec45a0e8a7c2e
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-06-08T10:04:10Z
  date_updated: 2021-06-08T10:04:10Z
  file_id: '9534'
  file_name: 2021_Cell_Petridou.pdf
  file_size: 11405875
  relation: main_file
  success: 1
file_date_updated: 2021-06-08T10:04:10Z
has_accepted_license: '1'
intvolume: '       184'
isi: 1
issue: '7'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1914-1928.e19
pmid: 1
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 2693FD8C-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: V00736
  name: Tissue material properties in embryonic development
publication: Cell
publication_identifier:
  eissn:
  - '10974172'
  issn:
  - '00928674'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/embryonic-tissue-undergoes-phase-transition/
scopus_import: '1'
status: public
title: Rigidity percolation uncovers a structural basis for embryonic tissue phase
  transitions
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 184
year: '2021'
...
---
_id: '9349'
abstract:
- lang: eng
  text: 'The way in which interactions between mechanics and biochemistry lead to
    the emergence of complex cell and tissue organization is an old question that
    has recently attracted renewed interest from biologists, physicists, mathematicians
    and computer scientists. Rapid advances in optical physics, microscopy and computational
    image analysis have greatly enhanced our ability to observe and quantify spatiotemporal
    patterns of signalling, force generation, deformation, and flow in living cells
    and tissues. Powerful new tools for genetic, biophysical and optogenetic manipulation
    are allowing us to perturb the underlying machinery that generates these patterns
    in increasingly sophisticated ways. Rapid advances in theory and computing have
    made it possible to construct predictive models that describe how cell and tissue
    organization and dynamics emerge from the local coupling of biochemistry and mechanics.
    Together, these advances have opened up a wealth of new opportunities to explore
    how mechanochemical patterning shapes organismal development. In this roadmap,
    we present a series of forward-looking case studies on mechanochemical patterning
    in development, written by scientists working at the interface between the physical
    and biological sciences, and covering a wide range of spatial and temporal scales,
    organisms, and modes of development. Together, these contributions highlight the
    many ways in which the dynamic coupling of mechanics and biochemistry shapes biological
    dynamics: from mechanoenzymes that sense force to tune their activity and motor
    output, to collectives of cells in tissues that flow and redistribute biochemical
    signals during development.'
acknowledgement: The AK group is supported by IST Austria and by the ERC under European
  Union Horizon 2020 research and innovation programme Grant 680037. Apologies to
  those whose work could not be mentioned due to limited space. We thank all my lab
  members, both past and present, for stimulating discussion. This work was funded
  by a Singapore Ministry of Education Tier 3 Grant, MOE2016-T3-1-005. We thank Francis
  Corson for continuous discussion and collaboration contributing to these views and
  for figure 4(A). PC is sponsored by the Institut Pasteur and the European Union's
  Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie
  Grant Agreement No. 665807. Research in JG's laboratory is funded by the European
  Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC
  Grant Agreement No. 337635, Institut Pasteur, CNRS, Cercle FSER, Fondation pour
  la Recherche Medicale, the Vallee Foundation and the ANR-19-CE-13-0024 Grant. We
  thank Erez Braun and Alex Mogilner for comments on the manuscript and Niv Ierushalmi
  for help with figure 5. This project has received funding from the European Union's
  Horizon 2020 research and innovation programme under Grant Agreement No. ERC-2018-COG
  Grant 819174-HydraMechanics awarded to KK. EH thanks all lab members, as well as
  Pierre Recho, Tsuyoshi Hirashima, Diana Pinheiro and Carl-Philip Heisenberg, for
  fruitful discussions on these topics—and apologize for not being able to cite many
  very relevant publications due to the strict 10-reference limit. EH acknowledges
  the support of Austrian Science Fund (FWF) (P 31639) and the European Research Council
  under the European Union's Horizon 2020 Research and Innovation Programme Grant
  Agreements (851288). The authors acknowledge the inspiring scientists whose work
  could not be cited in this perspective due to space constraints; the members of
  the Gartner Lab for helpful discussions; the Barbara and Gerson Bakar Foundation,
  the Chan Zuckerberg Biohub Investigators Programme, the National Institute of Health,
  and the Centre for Cellular Construction, an NSF Science and Technology Centre.
  The Minc laboratory is currently funded by the CNRS and the European Research Council
  (CoG Forcaster No. 647073). Research in the lab of J-LM is supported by the Institut
  Curie, the Centre National de la Recherche Scientifique (CNRS), the Institut National
  de la Santé Et de la Recherche Médicale (INSERM), and is funded by grants from the
  ATIP-Avenir programme, the Fondation Schlumberger pour l'Éducation et la Recherche
  via the Fondation pour la Recherche Médicale, the European Research Council Starting
  Grant ERC-2017-StG 757557, the European Molecular Biology Organization Young Investigator
  programme (EMBO YIP), the INSERM transversal programme Human Development Cell Atlas
  (HuDeCA), Paris Sciences Lettres (PSL) 'nouvelle équipe' and QLife (17-CONV-0005)
  grants and Labex DEEP (ANR-11-LABX-0044) which are part of the IDEX PSL (ANR-10-IDEX-0001-02).
  We acknowledge useful discussions with Massimo Vergassola, Sebastian Streichan and
  my lab members. Work in my laboratory on Drosophila embryogenesis is partly supported
  by NIH-R01GM122936. The authors acknowledge the support by a grant from the European
  Research Council (Grant No. 682161). Lenne group is funded by a grant from the 'Investissements
  d'Avenir' French Government programme managed by the French National Research Agency
  (ANR-16-CONV-0001) and by the Excellence Initiative of Aix-Marseille University—A*MIDEX,
  and ANR projects MechaResp (ANR-17-CE13-0032) and AdGastrulo (ANR-19-CE13-0022).
article_number: '041501'
article_processing_charge: No
article_type: original
author:
- first_name: Pierre François
  full_name: Lenne, Pierre François
  last_name: Lenne
- first_name: Edwin
  full_name: Munro, Edwin
  last_name: Munro
- first_name: Idse
  full_name: Heemskerk, Idse
  last_name: Heemskerk
- first_name: Aryeh
  full_name: Warmflash, Aryeh
  last_name: Warmflash
- first_name: Laura
  full_name: Bocanegra, Laura
  id: 4896F754-F248-11E8-B48F-1D18A9856A87
  last_name: Bocanegra
- first_name: Kasumi
  full_name: Kishi, Kasumi
  id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
  last_name: Kishi
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
- first_name: Yuchen
  full_name: Long, Yuchen
  last_name: Long
- first_name: Antoine
  full_name: Fruleux, Antoine
  last_name: Fruleux
- first_name: Arezki
  full_name: Boudaoud, Arezki
  last_name: Boudaoud
- first_name: Timothy E.
  full_name: Saunders, Timothy E.
  last_name: Saunders
- first_name: Paolo
  full_name: Caldarelli, Paolo
  last_name: Caldarelli
- first_name: Arthur
  full_name: Michaut, Arthur
  last_name: Michaut
- first_name: Jerome
  full_name: Gros, Jerome
  last_name: Gros
- first_name: Yonit
  full_name: Maroudas-Sacks, Yonit
  last_name: Maroudas-Sacks
- first_name: Kinneret
  full_name: Keren, Kinneret
  last_name: Keren
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Zev J.
  full_name: Gartner, Zev J.
  last_name: Gartner
- first_name: Benjamin
  full_name: Stormo, Benjamin
  last_name: Stormo
- first_name: Amy
  full_name: Gladfelter, Amy
  last_name: Gladfelter
- first_name: Alan
  full_name: Rodrigues, Alan
  last_name: Rodrigues
- first_name: Amy
  full_name: Shyer, Amy
  last_name: Shyer
- first_name: Nicolas
  full_name: Minc, Nicolas
  last_name: Minc
- first_name: Jean Léon
  full_name: Maître, Jean Léon
  last_name: Maître
- first_name: Stefano
  full_name: Di Talia, Stefano
  last_name: Di Talia
- first_name: Bassma
  full_name: Khamaisi, Bassma
  last_name: Khamaisi
- first_name: David
  full_name: Sprinzak, David
  last_name: Sprinzak
- first_name: Sham
  full_name: Tlili, Sham
  last_name: Tlili
citation:
  ama: Lenne PF, Munro E, Heemskerk I, et al. Roadmap for the multiscale coupling
    of biochemical and mechanical signals during development. <i>Physical biology</i>.
    2021;18(4). doi:<a href="https://doi.org/10.1088/1478-3975/abd0db">10.1088/1478-3975/abd0db</a>
  apa: Lenne, P. F., Munro, E., Heemskerk, I., Warmflash, A., Bocanegra, L., Kishi,
    K., … Tlili, S. (2021). Roadmap for the multiscale coupling of biochemical and
    mechanical signals during development. <i>Physical Biology</i>. IOP Publishing.
    <a href="https://doi.org/10.1088/1478-3975/abd0db">https://doi.org/10.1088/1478-3975/abd0db</a>
  chicago: Lenne, Pierre François, Edwin Munro, Idse Heemskerk, Aryeh Warmflash, Laura
    Bocanegra, Kasumi Kishi, Anna Kicheva, et al. “Roadmap for the Multiscale Coupling
    of Biochemical and Mechanical Signals during Development.” <i>Physical Biology</i>.
    IOP Publishing, 2021. <a href="https://doi.org/10.1088/1478-3975/abd0db">https://doi.org/10.1088/1478-3975/abd0db</a>.
  ieee: P. F. Lenne <i>et al.</i>, “Roadmap for the multiscale coupling of biochemical
    and mechanical signals during development,” <i>Physical biology</i>, vol. 18,
    no. 4. IOP Publishing, 2021.
  ista: Lenne PF, Munro E, Heemskerk I, Warmflash A, Bocanegra L, Kishi K, Kicheva
    A, Long Y, Fruleux A, Boudaoud A, Saunders TE, Caldarelli P, Michaut A, Gros J,
    Maroudas-Sacks Y, Keren K, Hannezo EB, Gartner ZJ, Stormo B, Gladfelter A, Rodrigues
    A, Shyer A, Minc N, Maître JL, Di Talia S, Khamaisi B, Sprinzak D, Tlili S. 2021.
    Roadmap for the multiscale coupling of biochemical and mechanical signals during
    development. Physical biology. 18(4), 041501.
  mla: Lenne, Pierre François, et al. “Roadmap for the Multiscale Coupling of Biochemical
    and Mechanical Signals during Development.” <i>Physical Biology</i>, vol. 18,
    no. 4, 041501, IOP Publishing, 2021, doi:<a href="https://doi.org/10.1088/1478-3975/abd0db">10.1088/1478-3975/abd0db</a>.
  short: P.F. Lenne, E. Munro, I. Heemskerk, A. Warmflash, L. Bocanegra, K. Kishi,
    A. Kicheva, Y. Long, A. Fruleux, A. Boudaoud, T.E. Saunders, P. Caldarelli, A.
    Michaut, J. Gros, Y. Maroudas-Sacks, K. Keren, E.B. Hannezo, Z.J. Gartner, B.
    Stormo, A. Gladfelter, A. Rodrigues, A. Shyer, N. Minc, J.L. Maître, S. Di Talia,
    B. Khamaisi, D. Sprinzak, S. Tlili, Physical Biology 18 (2021).
date_created: 2021-04-25T22:01:29Z
date_published: 2021-04-14T00:00:00Z
date_updated: 2023-08-08T13:15:46Z
day: '14'
ddc:
- '570'
department:
- _id: AnKi
- _id: EdHa
doi: 10.1088/1478-3975/abd0db
ec_funded: 1
external_id:
  isi:
  - '000640396400001'
  pmid:
  - '33276350'
file:
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  checksum: 4f52082549d3561c4c15d4d8d84ca5d8
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-04-27T08:38:35Z
  date_updated: 2021-04-27T08:38:35Z
  file_id: '9355'
  file_name: 2021_PhysBio_Lenne.pdf
  file_size: 6296324
  relation: main_file
  success: 1
file_date_updated: 2021-04-27T08:38:35Z
has_accepted_license: '1'
intvolume: '        18'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: B6FC0238-B512-11E9-945C-1524E6697425
  call_identifier: H2020
  grant_number: '680037'
  name: Coordination of Patterning And Growth In the Spinal Cord
- _id: 268294B6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31639
  name: Active mechano-chemical description of the cell cytoskeleton
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Physical biology
publication_identifier:
  eissn:
  - 1478-3975
publication_status: published
publisher: IOP Publishing
quality_controlled: '1'
related_material:
  record:
  - id: '13081'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Roadmap for the multiscale coupling of biochemical and mechanical signals during
  development
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2021'
...
---
_id: '9629'
abstract:
- lang: eng
  text: Intestinal organoids derived from single cells undergo complex crypt–villus
    patterning and morphogenesis. However, the nature and coordination of the underlying
    forces remains poorly characterized. Here, using light-sheet microscopy and large-scale
    imaging quantification, we demonstrate that crypt formation coincides with a stark
    reduction in lumen volume. We develop a 3D biophysical model to computationally
    screen different mechanical scenarios of crypt morphogenesis. Combining this with
    live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven
    crypt apical contraction and villus basal tension work synergistically with lumen
    volume reduction to drive crypt morphogenesis, and demonstrate the existence of
    a critical point in differential tensions above which crypt morphology becomes
    robust to volume changes. Finally, we identified a sodium/glucose cotransporter
    that is specific to differentiated enterocytes that modulates lumen volume reduction
    through cell swelling in the villus region. Together, our study uncovers the cellular
    basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust
    morphogenesis.
acknowledgement: 'We acknowledge the members of the Lennon-Duménil laboratory for
  sharing the mouse line of Myh9-GFP. We are grateful to the members of the Liberali
  laboratory and the FMI facilities for their support. We thank E. Tagliavini for
  IT support; L. Gelman for assistance and training; S. Bichet and A. Bogucki for
  helping with histology of mouse tissues; H. Kohler for fluorescence-activated cell
  sorting; G. Q. G. de Medeiros for maintenance of light-sheet microscopy; M. G. Stadler
  for scRNA-seq analysis; G. Gay for discussions on the 3D vertex model; the members
  of the Liberali laboratory, C. P. Heisenberg and C. Tsiairis for reading and providing
  feedback on the manuscript. Funding: Q.Y. is supported by a Postdoc fellowship from
  Peter und Taul Engelhorn Stiftung (PTES). This work received funding from the European
  Research Council (ERC) under the EU Horizon 2020 research and Innovation Programme
  Grant Agreement no. 758617 (to P.L.), the Swiss National Foundation (SNF) (POOP3_157531,
  to P.L.) and from the ERC under the EU Horizon 2020 Research and Innovation Program
  Grant Agreements 851288 (to E.H.) and the Austrian Science Fund (FWF) (P31639, to
  E.H.).'
article_processing_charge: No
article_type: original
author:
- first_name: Qiutan
  full_name: Yang, Qiutan
  last_name: Yang
- first_name: Shi-lei
  full_name: Xue, Shi-lei
  id: 31D2C804-F248-11E8-B48F-1D18A9856A87
  last_name: Xue
- first_name: Chii Jou
  full_name: Chan, Chii Jou
  last_name: Chan
- first_name: Markus
  full_name: Rempfler, Markus
  last_name: Rempfler
- first_name: Dario
  full_name: Vischi, Dario
  last_name: Vischi
- first_name: Francisca
  full_name: Maurer-Gutierrez, Francisca
  last_name: Maurer-Gutierrez
- first_name: Takashi
  full_name: Hiiragi, Takashi
  last_name: Hiiragi
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Prisca
  full_name: Liberali, Prisca
  last_name: Liberali
citation:
  ama: Yang Q, Xue S, Chan CJ, et al. Cell fate coordinates mechano-osmotic forces
    in intestinal crypt formation. <i>Nature Cell Biology</i>. 2021;23:733–744. doi:<a
    href="https://doi.org/10.1038/s41556-021-00700-2">10.1038/s41556-021-00700-2</a>
  apa: Yang, Q., Xue, S., Chan, C. J., Rempfler, M., Vischi, D., Maurer-Gutierrez,
    F., … Liberali, P. (2021). Cell fate coordinates mechano-osmotic forces in intestinal
    crypt formation. <i>Nature Cell Biology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41556-021-00700-2">https://doi.org/10.1038/s41556-021-00700-2</a>
  chicago: Yang, Qiutan, Shi-lei Xue, Chii Jou Chan, Markus Rempfler, Dario Vischi,
    Francisca Maurer-Gutierrez, Takashi Hiiragi, Edouard B Hannezo, and Prisca Liberali.
    “Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal Crypt Formation.”
    <i>Nature Cell Biology</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41556-021-00700-2">https://doi.org/10.1038/s41556-021-00700-2</a>.
  ieee: Q. Yang <i>et al.</i>, “Cell fate coordinates mechano-osmotic forces in intestinal
    crypt formation,” <i>Nature Cell Biology</i>, vol. 23. Springer Nature, pp. 733–744,
    2021.
  ista: Yang Q, Xue S, Chan CJ, Rempfler M, Vischi D, Maurer-Gutierrez F, Hiiragi
    T, Hannezo EB, Liberali P. 2021. Cell fate coordinates mechano-osmotic forces
    in intestinal crypt formation. Nature Cell Biology. 23, 733–744.
  mla: Yang, Qiutan, et al. “Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal
    Crypt Formation.” <i>Nature Cell Biology</i>, vol. 23, Springer Nature, 2021,
    pp. 733–744, doi:<a href="https://doi.org/10.1038/s41556-021-00700-2">10.1038/s41556-021-00700-2</a>.
  short: Q. Yang, S. Xue, C.J. Chan, M. Rempfler, D. Vischi, F. Maurer-Gutierrez,
    T. Hiiragi, E.B. Hannezo, P. Liberali, Nature Cell Biology 23 (2021) 733–744.
date_created: 2021-07-04T22:01:25Z
date_published: 2021-06-21T00:00:00Z
date_updated: 2023-08-10T13:57:36Z
day: '21'
department:
- _id: EdHa
doi: 10.1038/s41556-021-00700-2
ec_funded: 1
external_id:
  isi:
  - '000664016300003'
  pmid:
  - '34155381'
intvolume: '        23'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.biorxiv.org/content/10.1101/2020.05.13.094359
month: '06'
oa: 1
oa_version: Preprint
page: 733–744
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 268294B6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31639
  name: Active mechano-chemical description of the cell cytoskeleton
publication: Nature Cell Biology
publication_identifier:
  eissn:
  - 1476-4679
  issn:
  - 1465-7392
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 23
year: '2021'
...
---
_id: '10365'
abstract:
- lang: eng
  text: The early development of many organisms involves the folding of cell monolayers,
    but this behaviour is difficult to reproduce in vitro; therefore, both mechanistic
    causes and effects of local curvature remain unclear. Here we study epithelial
    cell monolayers on corrugated hydrogels engineered into wavy patterns, examining
    how concave and convex curvatures affect cellular and nuclear shape. We find that
    substrate curvature affects monolayer thickness, which is larger in valleys than
    crests. We show that this feature generically arises in a vertex model, leading
    to the hypothesis that cells may sense curvature by modifying the thickness of
    the tissue. We find that local curvature also affects nuclear morphology and positioning,
    which we explain by extending the vertex model to take into account membrane–nucleus
    interactions, encoding thickness modulation in changes to nuclear deformation
    and position. We propose that curvature governs the spatial distribution of yes-associated
    proteins via nuclear shape and density changes. We show that curvature also induces
    significant variations in lamins, chromatin condensation and cell proliferation
    rate in folded epithelial tissues. Together, this work identifies active cell
    mechanics and nuclear mechanoadaptation as the key players of the mechanistic
    regulation of epithelia to substrate curvature.
acknowledgement: S.G. acknowledges funding from FEDER Prostem Research Project no.
  1510614 (Wallonia DG06), F.R.S.-FNRS Epiforce Research Project no. T.0092.21 and
  Interreg MAT(T)ISSE project, which is financially supported by Interreg France-Wallonie-Vlaanderen
  (Fonds Européen de Développement Régional, FEDER-ERDF). This project was supported
  by the European Research Council under the European Union’s Horizon 2020 Research
  and Innovation Programme grant agreement 851288 (to E.H.), and by the Austrian Science
  Fund (FWF) (P 31639; to E.H.). L.R.M. acknowledges funding from the Agence National
  de la Recherche (ANR), as part of the ‘Investments d’Avenir’ Programme (I-SITE ULNE/ANR-16-IDEX-0004
  ULNE). This work benefited from ANR-10-EQPX-04-01 and FEDER 12001407 grants to F.L.
  W.D.V. is supported by the Research Foundation Flanders (FWO 1516619N, FWO GOO5819N,
  FWO I003420N, FWO IRI I000321N) and is member of the Research Excellence Consortium
  µNEURO at the University of Antwerp. M.L. is financially supported by FRIA (F.R.S.-FNRS).
  M.S. is a Senior Research Associate of the Fund for Scientific Research (F.R.S.-FNRS)
  and acknowledges EOS grant no. 30650939 (PRECISION). Sketches in Figs. 1a and 5e
  and Extended Data Fig. 9 were drawn by C. Levicek.
article_processing_charge: No
article_type: original
author:
- first_name: Marine
  full_name: Luciano, Marine
  last_name: Luciano
- first_name: Shi-lei
  full_name: Xue, Shi-lei
  id: 31D2C804-F248-11E8-B48F-1D18A9856A87
  last_name: Xue
- first_name: Winnok H.
  full_name: De Vos, Winnok H.
  last_name: De Vos
- first_name: Lorena
  full_name: Redondo-Morata, Lorena
  last_name: Redondo-Morata
- first_name: Mathieu
  full_name: Surin, Mathieu
  last_name: Surin
- first_name: Frank
  full_name: Lafont, Frank
  last_name: Lafont
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Sylvain
  full_name: Gabriele, Sylvain
  last_name: Gabriele
citation:
  ama: Luciano M, Xue S, De Vos WH, et al. Cell monolayers sense curvature by exploiting
    active mechanics and nuclear mechanoadaptation. <i>Nature Physics</i>. 2021;17(12):1382–1390.
    doi:<a href="https://doi.org/10.1038/s41567-021-01374-1">10.1038/s41567-021-01374-1</a>
  apa: Luciano, M., Xue, S., De Vos, W. H., Redondo-Morata, L., Surin, M., Lafont,
    F., … Gabriele, S. (2021). Cell monolayers sense curvature by exploiting active
    mechanics and nuclear mechanoadaptation. <i>Nature Physics</i>. Springer Nature.
    <a href="https://doi.org/10.1038/s41567-021-01374-1">https://doi.org/10.1038/s41567-021-01374-1</a>
  chicago: Luciano, Marine, Shi-lei Xue, Winnok H. De Vos, Lorena Redondo-Morata,
    Mathieu Surin, Frank Lafont, Edouard B Hannezo, and Sylvain Gabriele. “Cell Monolayers
    Sense Curvature by Exploiting Active Mechanics and Nuclear Mechanoadaptation.”
    <i>Nature Physics</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41567-021-01374-1">https://doi.org/10.1038/s41567-021-01374-1</a>.
  ieee: M. Luciano <i>et al.</i>, “Cell monolayers sense curvature by exploiting active
    mechanics and nuclear mechanoadaptation,” <i>Nature Physics</i>, vol. 17, no.
    12. Springer Nature, pp. 1382–1390, 2021.
  ista: Luciano M, Xue S, De Vos WH, Redondo-Morata L, Surin M, Lafont F, Hannezo
    EB, Gabriele S. 2021. Cell monolayers sense curvature by exploiting active mechanics
    and nuclear mechanoadaptation. Nature Physics. 17(12), 1382–1390.
  mla: Luciano, Marine, et al. “Cell Monolayers Sense Curvature by Exploiting Active
    Mechanics and Nuclear Mechanoadaptation.” <i>Nature Physics</i>, vol. 17, no.
    12, Springer Nature, 2021, pp. 1382–1390, doi:<a href="https://doi.org/10.1038/s41567-021-01374-1">10.1038/s41567-021-01374-1</a>.
  short: M. Luciano, S. Xue, W.H. De Vos, L. Redondo-Morata, M. Surin, F. Lafont,
    E.B. Hannezo, S. Gabriele, Nature Physics 17 (2021) 1382–1390.
date_created: 2021-11-28T23:01:29Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2023-10-16T06:31:54Z
day: '18'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.1038/s41567-021-01374-1
ec_funded: 1
external_id:
  isi:
  - '000720204300004'
file:
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  checksum: 5d6d76750a71d7cb632bb15417c38ef7
  content_type: application/pdf
  creator: channezo
  date_created: 2023-10-11T09:31:43Z
  date_updated: 2023-10-11T09:31:43Z
  file_id: '14420'
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  file_size: 40285498
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file_date_updated: 2023-10-11T09:31:43Z
has_accepted_license: '1'
intvolume: '        17'
isi: 1
issue: '12'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: 1382–1390
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 268294B6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31639
  name: Active mechano-chemical description of the cell cytoskeleton
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Webpage
    relation: press_release
    url: https://ist.ac.at/en/news/how-cells-feel-curvature/
scopus_import: '1'
status: public
title: Cell monolayers sense curvature by exploiting active mechanics and nuclear
  mechanoadaptation
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2021'
...
---
_id: '10402'
abstract:
- lang: eng
  text: Branching morphogenesis governs the formation of many organs such as lung,
    kidney, and the neurovascular system. Many studies have explored system-specific
    molecular and cellular regulatory mechanisms, as well as self-organizing rules
    underlying branching morphogenesis. However, in addition to local cues, branched
    tissue growth can also be influenced by global guidance. Here, we develop a theoretical
    framework for a stochastic self-organized branching process in the presence of
    external cues. Combining analytical theory with numerical simulations, we predict
    differential signatures of global vs. local regulatory mechanisms on the branching
    pattern, such as angle distributions, domain size, and space-filling efficiency.
    We find that branch alignment follows a generic scaling law determined by the
    strength of global guidance, while local interactions influence the tissue density
    but not its overall territory. Finally, using zebrafish innervation as a model
    system, we test these key features of the model experimentally. Our work thus
    provides quantitative predictions to disentangle the role of different types of
    cues in shaping branched structures across scales.
acknowledgement: We thank all members of our respective groups for helpful discussion
  on the paper. The authors are also grateful to Prof. Abdel El. Manira for support
  and sharing Tg(HUC:Gal4;UAS:Synaptohysin-GFP), to Haohao Wu for discussion, and
  thank Elena Zabalueva for the zebrafish schematic. The authors also acknowledge
  Zebrafish core facility, Genome Engineering Zebrafish and Biomedicum Imaging Core
  from the Karolinska Institutet for technical support. This work received funding
  from the ERC under the European Union’s Horizon 2020 research and innovation programme
  (grant agreement No. 851288 to E.H.) and under the Marie Skłodowska-Curie grant
  agreement No. 754411 (to M.C.U.); Swedish Research Council (to F.L., I.A. and S.H.);
  Knut and Alice Wallenberg Foundation (F.L. and I.A.); Swedish Brain Foundation (F.L.
  and S.H.); Ming Wai Lau Foundation (to F.L.); StratRegen (to F.L.); ERC Consolidator
  grant STEMMING-FROM-NERVE and ERC Synergy Grant KILL-OR-DIFFERENTIATE (to I.A.);
  Bertil Hallsten Research Foundation (to I.A.); Cancerfonden (to I.A.); the Paradifference
  Foundation (to I.A.); Austrian Science Fund (to I.A.); and StratNeuro (to S.H.).
article_number: '6830'
article_processing_charge: No
article_type: original
author:
- first_name: Mehmet C
  full_name: Ucar, Mehmet C
  id: 50B2A802-6007-11E9-A42B-EB23E6697425
  last_name: Ucar
  orcid: 0000-0003-0506-4217
- first_name: Dmitrii
  full_name: Kamenev, Dmitrii
  last_name: Kamenev
- first_name: Kazunori
  full_name: Sunadome, Kazunori
  last_name: Sunadome
- first_name: Dominik C
  full_name: Fachet, Dominik C
  id: 14FDD550-AA41-11E9-A0E5-1ACCE5697425
  last_name: Fachet
- first_name: Francois
  full_name: Lallemend, Francois
  last_name: Lallemend
- first_name: Igor
  full_name: Adameyko, Igor
  last_name: Adameyko
- first_name: Saida
  full_name: Hadjab, Saida
  last_name: Hadjab
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Ucar MC, Kamenev D, Sunadome K, et al. Theory of branching morphogenesis by
    local interactions and global guidance. <i>Nature Communications</i>. 2021;12.
    doi:<a href="https://doi.org/10.1038/s41467-021-27135-5">10.1038/s41467-021-27135-5</a>
  apa: Ucar, M. C., Kamenev, D., Sunadome, K., Fachet, D. C., Lallemend, F., Adameyko,
    I., … Hannezo, E. B. (2021). Theory of branching morphogenesis by local interactions
    and global guidance. <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-021-27135-5">https://doi.org/10.1038/s41467-021-27135-5</a>
  chicago: Ucar, Mehmet C, Dmitrii Kamenev, Kazunori Sunadome, Dominik C Fachet, Francois
    Lallemend, Igor Adameyko, Saida Hadjab, and Edouard B Hannezo. “Theory of Branching
    Morphogenesis by Local Interactions and Global Guidance.” <i>Nature Communications</i>.
    Springer Nature, 2021. <a href="https://doi.org/10.1038/s41467-021-27135-5">https://doi.org/10.1038/s41467-021-27135-5</a>.
  ieee: M. C. Ucar <i>et al.</i>, “Theory of branching morphogenesis by local interactions
    and global guidance,” <i>Nature Communications</i>, vol. 12. Springer Nature,
    2021.
  ista: Ucar MC, Kamenev D, Sunadome K, Fachet DC, Lallemend F, Adameyko I, Hadjab
    S, Hannezo EB. 2021. Theory of branching morphogenesis by local interactions and
    global guidance. Nature Communications. 12, 6830.
  mla: Ucar, Mehmet C., et al. “Theory of Branching Morphogenesis by Local Interactions
    and Global Guidance.” <i>Nature Communications</i>, vol. 12, 6830, Springer Nature,
    2021, doi:<a href="https://doi.org/10.1038/s41467-021-27135-5">10.1038/s41467-021-27135-5</a>.
  short: M.C. Ucar, D. Kamenev, K. Sunadome, D.C. Fachet, F. Lallemend, I. Adameyko,
    S. Hadjab, E.B. Hannezo, Nature Communications 12 (2021).
date_created: 2021-12-05T23:01:40Z
date_published: 2021-11-24T00:00:00Z
date_updated: 2023-08-14T13:18:46Z
day: '24'
ddc:
- '573'
department:
- _id: EdHa
doi: 10.1038/s41467-021-27135-5
ec_funded: 1
external_id:
  isi:
  - '000722322900020'
  pmid:
  - '34819507'
file:
- access_level: open_access
  checksum: 63c56ec75314a71e63e7dd2920b3c5b5
  content_type: application/pdf
  creator: cchlebak
  date_created: 2021-12-10T08:54:09Z
  date_updated: 2021-12-10T08:54:09Z
  file_id: '10529'
  file_name: 2021_NatComm_Ucar.pdf
  file_size: 2303405
  relation: main_file
  success: 1
file_date_updated: 2021-12-10T08:54:09Z
has_accepted_license: '1'
intvolume: '        12'
isi: 1
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  record:
  - id: '13058'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Theory of branching morphogenesis by local interactions and global guidance
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '8220'
abstract:
- lang: eng
  text: Understanding to what extent stem cell potential is a cell-intrinsic property
    or an emergent behavior coming from global tissue dynamics and geometry is a key
    outstanding question of systems and stem cell biology. Here, we propose a theory
    of stem cell dynamics as a stochastic competition for access to a spatially localized
    niche, giving rise to a stochastic conveyor-belt model. Cell divisions produce
    a steady cellular stream which advects cells away from the niche, while random
    rearrangements enable cells away from the niche to be favorably repositioned.
    Importantly, even when assuming that all cells in a tissue are molecularly equivalent,
    we predict a common (“universal”) functional dependence of the long-term clonal
    survival probability on distance from the niche, as well as the emergence of a
    well-defined number of functional stem cells, dependent only on the rate of random
    movements vs. mitosis-driven advection. We test the predictions of this theory
    on datasets of pubertal mammary gland tips and embryonic kidney tips, as well
    as homeostatic intestinal crypts. Importantly, we find good agreement for the
    predicted functional dependency of the competition as a function of position,
    and thus functional stem cell number in each organ. This argues for a key role
    of positional fluctuations in dictating stem cell number and dynamics, and we
    discuss the applicability of this theory to other settings.
acknowledgement: "We thank all members of the E.H., B.D.S., and J.v.R. groups for
  stimulating discussions. This project was supported by\r\nthe European Research
  Council (648804 to J.v.R. and 851288 to E.H.). It has also received support from
  the CancerGenomics.nl (Netherlands Organization for Scientific Research) program
  (J.v.R.) and the Doctor Josef Steiner Foundation (J.v.R). B.D.S. was supported by
  Royal Society E. P. Abraham Research Professorship RP/R1/180165 and Wellcome Trust
  Grant 098357/Z/12/Z."
article_processing_charge: No
article_type: original
author:
- first_name: Bernat
  full_name: Corominas-Murtra, Bernat
  id: 43BE2298-F248-11E8-B48F-1D18A9856A87
  last_name: Corominas-Murtra
  orcid: 0000-0001-9806-5643
- first_name: Colinda L.G.J.
  full_name: Scheele, Colinda L.G.J.
  last_name: Scheele
- first_name: Kasumi
  full_name: Kishi, Kasumi
  id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
  last_name: Kishi
- first_name: Saskia I.J.
  full_name: Ellenbroek, Saskia I.J.
  last_name: Ellenbroek
- first_name: Benjamin D.
  full_name: Simons, Benjamin D.
  last_name: Simons
- first_name: Jacco
  full_name: Van Rheenen, Jacco
  last_name: Van Rheenen
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
citation:
  ama: Corominas-Murtra B, Scheele CLGJ, Kishi K, et al. Stem cell lineage survival
    as a noisy competition for niche access. <i>Proceedings of the National Academy
    of Sciences of the United States of America</i>. 2020;117(29):16969-16975. doi:<a
    href="https://doi.org/10.1073/pnas.1921205117">10.1073/pnas.1921205117</a>
  apa: Corominas-Murtra, B., Scheele, C. L. G. J., Kishi, K., Ellenbroek, S. I. J.,
    Simons, B. D., Van Rheenen, J., &#38; Hannezo, E. B. (2020). Stem cell lineage
    survival as a noisy competition for niche access. <i>Proceedings of the National
    Academy of Sciences of the United States of America</i>. National Academy of Sciences.
    <a href="https://doi.org/10.1073/pnas.1921205117">https://doi.org/10.1073/pnas.1921205117</a>
  chicago: Corominas-Murtra, Bernat, Colinda L.G.J. Scheele, Kasumi Kishi, Saskia
    I.J. Ellenbroek, Benjamin D. Simons, Jacco Van Rheenen, and Edouard B Hannezo.
    “Stem Cell Lineage Survival as a Noisy Competition for Niche Access.” <i>Proceedings
    of the National Academy of Sciences of the United States of America</i>. National
    Academy of Sciences, 2020. <a href="https://doi.org/10.1073/pnas.1921205117">https://doi.org/10.1073/pnas.1921205117</a>.
  ieee: B. Corominas-Murtra <i>et al.</i>, “Stem cell lineage survival as a noisy
    competition for niche access,” <i>Proceedings of the National Academy of Sciences
    of the United States of America</i>, vol. 117, no. 29. National Academy of Sciences,
    pp. 16969–16975, 2020.
  ista: Corominas-Murtra B, Scheele CLGJ, Kishi K, Ellenbroek SIJ, Simons BD, Van
    Rheenen J, Hannezo EB. 2020. Stem cell lineage survival as a noisy competition
    for niche access. Proceedings of the National Academy of Sciences of the United
    States of America. 117(29), 16969–16975.
  mla: Corominas-Murtra, Bernat, et al. “Stem Cell Lineage Survival as a Noisy Competition
    for Niche Access.” <i>Proceedings of the National Academy of Sciences of the United
    States of America</i>, vol. 117, no. 29, National Academy of Sciences, 2020, pp.
    16969–75, doi:<a href="https://doi.org/10.1073/pnas.1921205117">10.1073/pnas.1921205117</a>.
  short: B. Corominas-Murtra, C.L.G.J. Scheele, K. Kishi, S.I.J. Ellenbroek, B.D.
    Simons, J. Van Rheenen, E.B. Hannezo, Proceedings of the National Academy of Sciences
    of the United States of America 117 (2020) 16969–16975.
date_created: 2020-08-09T22:00:52Z
date_published: 2020-07-21T00:00:00Z
date_updated: 2023-08-22T08:29:30Z
day: '21'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1073/pnas.1921205117
ec_funded: 1
external_id:
  isi:
  - '000553292900014'
  pmid:
  - '32611816'
file:
- access_level: open_access
  content_type: application/pdf
  creator: dernst
  date_created: 2020-08-10T06:50:28Z
  date_updated: 2020-08-10T06:50:28Z
  file_id: '8223'
  file_name: 2020_PNAS_Corominas.pdf
  file_size: 1111604
  relation: main_file
  success: 1
file_date_updated: 2020-08-10T06:50:28Z
has_accepted_license: '1'
intvolume: '       117'
isi: 1
issue: '29'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 16969-16975
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
publication: Proceedings of the National Academy of Sciences of the United States
  of America
publication_identifier:
  eissn:
  - '10916490'
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
  link:
  - relation: press_release
    url: https://ist.ac.at/en/news/order-from-noise/
scopus_import: '1'
status: public
title: Stem cell lineage survival as a noisy competition for niche access
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 117
year: '2020'
...
