---
_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:
- access_level: open_access
  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'
  file_name: 50145_4_merged_1630498627.pdf
  file_size: 40285498
  relation: main_file
  success: 1
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: '6508'
abstract:
- lang: eng
  text: Segregation of maternal determinants within the oocyte constitutes the first
    step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming
    leads to the segregation of ooplasm from yolk granules along the animal-vegetal
    axis of the oocyte. Here, we show that this process does not rely on cortical
    actin reorganization, as previously thought, but instead on a cell-cycle-dependent
    bulk actin polymerization wave traveling from the animal to the vegetal pole of
    the oocyte. This wave functions in segregation by both pulling ooplasm animally
    and pushing yolk granules vegetally. Using biophysical experimentation and theory,
    we show that ooplasm pulling is mediated by bulk actin network flows exerting
    friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism
    closely resembling actin comet formation on yolk granules. Our study defines a
    novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte
    polarization via ooplasmic segregation.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We would like to thank Pierre Recho, Guillaume Salbreux, and Silvia
  Grigolon for advice on the theory, Lila Solnica-Krezel for kindly providing us with
  zebrafish dachsous mutants, members of the Heisenberg and Hannezo groups for fruitful
  discussions, and the Bioimaging and zebrafish facilities at IST Austria for their
  continuous support. This project has received funding from the European Union (European
  Research Council Advanced Grant 742573 to C.P.H.) and from the Austrian Science
  Fund (FWF) (P 31639 to E.H.).
article_processing_charge: No
article_type: original
author:
- first_name: Shayan
  full_name: Shamipour, Shayan
  id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
  last_name: Shamipour
- first_name: Roland
  full_name: Kardos, Roland
  id: 4039350E-F248-11E8-B48F-1D18A9856A87
  last_name: Kardos
- first_name: Shi-lei
  full_name: Xue, Shi-lei
  id: 31D2C804-F248-11E8-B48F-1D18A9856A87
  last_name: Xue
- first_name: Björn
  full_name: Hof, Björn
  id: 3A374330-F248-11E8-B48F-1D18A9856A87
  last_name: Hof
  orcid: 0000-0003-2057-2754
- 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: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. Bulk actin
    dynamics drive phase segregation in zebrafish oocytes. <i>Cell</i>. 2019;177(6):1463-1479.e18.
    doi:<a href="https://doi.org/10.1016/j.cell.2019.04.030">10.1016/j.cell.2019.04.030</a>
  apa: Shamipour, S., Kardos, R., Xue, S., Hof, B., Hannezo, E. B., &#38; Heisenberg,
    C.-P. J. (2019). Bulk actin dynamics drive phase segregation in zebrafish oocytes.
    <i>Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.cell.2019.04.030">https://doi.org/10.1016/j.cell.2019.04.030</a>
  chicago: Shamipour, Shayan, Roland Kardos, Shi-lei Xue, Björn Hof, Edouard B Hannezo,
    and Carl-Philipp J Heisenberg. “Bulk Actin Dynamics Drive Phase Segregation in
    Zebrafish Oocytes.” <i>Cell</i>. Elsevier, 2019. <a href="https://doi.org/10.1016/j.cell.2019.04.030">https://doi.org/10.1016/j.cell.2019.04.030</a>.
  ieee: S. Shamipour, R. Kardos, S. Xue, B. Hof, E. B. Hannezo, and C.-P. J. Heisenberg,
    “Bulk actin dynamics drive phase segregation in zebrafish oocytes,” <i>Cell</i>,
    vol. 177, no. 6. Elsevier, p. 1463–1479.e18, 2019.
  ista: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. 2019. Bulk
    actin dynamics drive phase segregation in zebrafish oocytes. Cell. 177(6), 1463–1479.e18.
  mla: Shamipour, Shayan, et al. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish
    Oocytes.” <i>Cell</i>, vol. 177, no. 6, Elsevier, 2019, p. 1463–1479.e18, doi:<a
    href="https://doi.org/10.1016/j.cell.2019.04.030">10.1016/j.cell.2019.04.030</a>.
  short: S. Shamipour, R. Kardos, S. Xue, B. Hof, E.B. Hannezo, C.-P.J. Heisenberg,
    Cell 177 (2019) 1463–1479.e18.
date_created: 2019-06-02T21:59:12Z
date_published: 2019-05-30T00:00:00Z
date_updated: 2024-03-25T23:30:21Z
day: '30'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
- _id: BjHo
doi: 10.1016/j.cell.2019.04.030
ec_funded: 1
external_id:
  isi:
  - '000469415100013'
  pmid:
  - '31080065'
file:
- access_level: open_access
  checksum: aea43726d80e35ce3885073a5f05c3e3
  content_type: application/pdf
  creator: dernst
  date_created: 2020-10-21T07:22:34Z
  date_updated: 2020-10-21T07:22:34Z
  file_id: '8686'
  file_name: 2019_Cell_Shamipour_accepted.pdf
  file_size: 3356292
  relation: main_file
  success: 1
file_date_updated: 2020-10-21T07:22:34Z
has_accepted_license: '1'
intvolume: '       177'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.cell.2019.04.030
month: '05'
oa: 1
oa_version: Published Version
page: 1463-1479.e18
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: 268294B6-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31639
  name: Active mechano-chemical description of the cell cytoskeleton
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/how-the-cytoplasm-separates-from-the-yolk/
  record:
  - id: '8350'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Bulk actin dynamics drive phase segregation in zebrafish oocytes
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 177
year: '2019'
...