---
_id: '12830'
abstract:
- lang: eng
text: Interstitial fluid (IF) accumulation between embryonic cells is thought to
be important for embryo patterning and morphogenesis. Here, we identify a positive
mechanical feedback loop between cell migration and IF relocalization and find
that it promotes embryonic axis formation during zebrafish gastrulation. We show
that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between
the yolk cell and deep cell tissue to extend the embryonic axis, compress the
overlying deep cell layer, thereby causing IF to flow from the deep cell layer
to the boundary between the yolk cell and the deep cell layer, directly ahead
of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion
formation and migration by opening up the space into which the ppl moves and,
thereby, the ability of the ppl to trigger IF relocalization by pushing against
the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic
feedback loop between cell migration and IF relocalization.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
acknowledgement: We thank Andrea Pauli (IMP) and Edouard Hannezo (ISTA) for fruitful
discussions and support with the SPIM experiments; the Heisenberg group, and especially
Feyza Nur Arslan and Alexandra Schauer, for discussions and feedback; Michaela Jović
(ISTA) for help with the quantitative real-time PCR protocol; the bioimaging and
zebrafish facilities of ISTA for continuous support; Stephan Preibisch (Janelia
Research Campus) for support with the SPIM data analysis; and Nobuhiro Nakamura
(Tokyo Institute of Technology) for sharing α1-Na+/K+-ATPase antibody. This work
was supported by funding from the European Union (European Research Council Advanced
grant 742573 to C.-P.H.), postdoctoral fellowships from EMBO (LTF-850-2017) and
HFSP (LT000429/2018-L2) to D.P., and a PhD fellowship from the Studienstiftung des
deutschen Volkes to F.P.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Karla
full_name: Huljev, Karla
id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87
last_name: Huljev
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- 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: Friedrich
full_name: Preusser, Friedrich
last_name: Preusser
- first_name: Irene
full_name: Steccari, Irene
id: 2705C766-9FE2-11EA-B224-C6773DDC885E
last_name: Steccari
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Suyash
full_name: Naik, Suyash
id: 2C0B105C-F248-11E8-B48F-1D18A9856A87
last_name: Naik
orcid: 0000-0001-8421-5508
- 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: Huljev K, Shamipour S, Nunes Pinheiro DC, et al. A hydraulic feedback loop
between mesendoderm cell migration and interstitial fluid relocalization promotes
embryonic axis formation in zebrafish. Developmental Cell. 2023;58(7):582-596.e7.
doi:10.1016/j.devcel.2023.02.016
apa: Huljev, K., Shamipour, S., Nunes Pinheiro, D. C., Preusser, F., Steccari, I.,
Sommer, C. M., … Heisenberg, C.-P. J. (2023). A hydraulic feedback loop between
mesendoderm cell migration and interstitial fluid relocalization promotes embryonic
axis formation in zebrafish. Developmental Cell. Elsevier. https://doi.org/10.1016/j.devcel.2023.02.016
chicago: Huljev, Karla, Shayan Shamipour, Diana C Nunes Pinheiro, Friedrich Preusser,
Irene Steccari, Christoph M Sommer, Suyash Naik, and Carl-Philipp J Heisenberg.
“A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial
Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” Developmental
Cell. Elsevier, 2023. https://doi.org/10.1016/j.devcel.2023.02.016.
ieee: K. Huljev et al., “A hydraulic feedback loop between mesendoderm cell
migration and interstitial fluid relocalization promotes embryonic axis formation
in zebrafish,” Developmental Cell, vol. 58, no. 7. Elsevier, p. 582–596.e7,
2023.
ista: Huljev K, Shamipour S, Nunes Pinheiro DC, Preusser F, Steccari I, Sommer CM,
Naik S, Heisenberg C-PJ. 2023. A hydraulic feedback loop between mesendoderm cell
migration and interstitial fluid relocalization promotes embryonic axis formation
in zebrafish. Developmental Cell. 58(7), 582–596.e7.
mla: Huljev, Karla, et al. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration
and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.”
Developmental Cell, vol. 58, no. 7, Elsevier, 2023, p. 582–596.e7, doi:10.1016/j.devcel.2023.02.016.
short: K. Huljev, S. Shamipour, D.C. Nunes Pinheiro, F. Preusser, I. Steccari, C.M.
Sommer, S. Naik, C.-P.J. Heisenberg, Developmental Cell 58 (2023) 582–596.e7.
date_created: 2023-04-16T22:01:07Z
date_published: 2023-04-10T00:00:00Z
date_updated: 2023-08-01T14:10:38Z
day: '10'
ddc:
- '570'
department:
- _id: CaHe
- _id: Bio
doi: 10.1016/j.devcel.2023.02.016
ec_funded: 1
external_id:
isi:
- '000982111800001'
file:
- access_level: open_access
checksum: c80ca2ebc241232aacdb5aa4b4c80957
content_type: application/pdf
creator: dernst
date_created: 2023-04-17T07:41:25Z
date_updated: 2023-04-17T07:41:25Z
file_id: '12842'
file_name: 2023_DevelopmentalCell_Huljev.pdf
file_size: 7925886
relation: main_file
success: 1
file_date_updated: 2023-04-17T07:41:25Z
has_accepted_license: '1'
intvolume: ' 58'
isi: 1
issue: '7'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 582-596.e7
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: 26520D1E-B435-11E9-9278-68D0E5697425
grant_number: ALTF 850-2017
name: Coordination of mesendoderm cell fate specification and internalization during
zebrafish gastrulation
- _id: 266BC5CE-B435-11E9-9278-68D0E5697425
grant_number: LT000429
name: Coordination of mesendoderm fate specification and internalization during
zebrafish gastrulation
publication: Developmental Cell
publication_identifier:
eissn:
- 1878-1551
issn:
- 1534-5807
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A hydraulic feedback loop between mesendoderm cell migration and interstitial
fluid relocalization promotes embryonic axis formation in zebrafish
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: 58
year: '2023'
...
---
_id: '10766'
abstract:
- lang: eng
text: Tension of the actomyosin cell cortex plays a key role in determining cell–cell
contact growth and size. The level of cortical tension outside of the cell–cell
contact, when pulling at the contact edge, scales with the total size to which
a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)].
Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic
relationship only applies to a narrow range of cortical tension increase and that
above a critical threshold, contact size inversely scales with cortical tension.
This switch from cortical tension increasing to decreasing progenitor cell–cell
contact size is caused by cortical tension promoting E-cadherin anchoring to the
actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin
at the contact. After tension-mediated E-cadherin stabilization at the contact
exceeds a critical threshold level, the rate by which the contact expands in response
to pulling forces from the cortex sharply drops, leading to smaller contacts at
physiologically relevant timescales of contact formation. Thus, the activity of
cortical tension in expanding cell–cell contact size is limited by tension-stabilizing
E-cadherin–actin complexes at the contact.
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: PreCl
acknowledgement: 'We thank Guillaume Salbreaux, Silvia Grigolon, Edouard Hannezo,
and Vanessa Barone for discussions and comments on the manuscript and Shayan Shamipour
and Daniel Capek for help with data analysis. We also thank the Imaging & Optics,
Electron Microscopy, and Zebrafish Facility Scientific Service Units at the Institute
of Science and Technology Austria (ISTA)Nasser Darwish-Miranda for continuous support.
We acknowledge Hitoshi Morita for the gift of VinculinB-GFP plasmid. This research
was supported by an ISTA Fellow Marie-Curie Co-funding of regional, national, and
international programmes Grant P_IST_EU01 (to J.S.), European Molecular Biology
Organization Long-Term Fellowship Grant, ALTF reference number: 187-2013 (to M.S.),
Schroedinger Fellowship J4332-B28 (to M.S.), and European Research Council Advanced
Grant (MECSPEC; to C.-P.H.).'
article_number: e2122030119
article_processing_charge: No
article_type: original
author:
- first_name: Jana
full_name: Slovakova, Jana
id: 30F3F2F0-F248-11E8-B48F-1D18A9856A87
last_name: Slovakova
- first_name: Mateusz K
full_name: Sikora, Mateusz K
id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87
last_name: Sikora
- first_name: Feyza N
full_name: Arslan, Feyza N
id: 49DA7910-F248-11E8-B48F-1D18A9856A87
last_name: Arslan
orcid: 0000-0001-5809-9566
- first_name: Silvia
full_name: Caballero Mancebo, Silvia
id: 2F1E1758-F248-11E8-B48F-1D18A9856A87
last_name: Caballero Mancebo
orcid: 0000-0002-5223-3346
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- 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: Slovakova J, Sikora MK, Arslan FN, et al. Tension-dependent stabilization of
E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor
cells. Proceedings of the National Academy of Sciences of the United States
of America. 2022;119(8). doi:10.1073/pnas.2122030119
apa: Slovakova, J., Sikora, M. K., Arslan, F. N., Caballero Mancebo, S., Krens,
G., Kaufmann, W., … Heisenberg, C.-P. J. (2022). Tension-dependent stabilization
of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor
cells. Proceedings of the National Academy of Sciences of the United States
of America. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2122030119
chicago: Slovakova, Jana, Mateusz K Sikora, Feyza N Arslan, Silvia Caballero Mancebo,
Gabriel Krens, Walter Kaufmann, Jack Merrin, and Carl-Philipp J Heisenberg. “Tension-Dependent
Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer
Progenitor Cells.” Proceedings of the National Academy of Sciences of the United
States of America. Proceedings of the National Academy of Sciences, 2022.
https://doi.org/10.1073/pnas.2122030119.
ieee: J. Slovakova et al., “Tension-dependent stabilization of E-cadherin
limits cell-cell contact expansion in zebrafish germ-layer progenitor cells,”
Proceedings of the National Academy of Sciences of the United States of America,
vol. 119, no. 8. Proceedings of the National Academy of Sciences, 2022.
ista: Slovakova J, Sikora MK, Arslan FN, Caballero Mancebo S, Krens G, Kaufmann
W, Merrin J, Heisenberg C-PJ. 2022. Tension-dependent stabilization of E-cadherin
limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings
of the National Academy of Sciences of the United States of America. 119(8), e2122030119.
mla: Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits
Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” Proceedings
of the National Academy of Sciences of the United States of America, vol.
119, no. 8, e2122030119, Proceedings of the National Academy of Sciences, 2022,
doi:10.1073/pnas.2122030119.
short: J. Slovakova, M.K. Sikora, F.N. Arslan, S. Caballero Mancebo, G. Krens, W.
Kaufmann, J. Merrin, C.-P.J. Heisenberg, Proceedings of the National Academy of
Sciences of the United States of America 119 (2022).
date_created: 2022-02-20T23:01:31Z
date_published: 2022-02-14T00:00:00Z
date_updated: 2023-08-02T14:26:51Z
day: '14'
ddc:
- '570'
department:
- _id: CaHe
- _id: EM-Fac
- _id: Bio
doi: 10.1073/pnas.2122030119
ec_funded: 1
external_id:
isi:
- '000766926900009'
file:
- access_level: open_access
checksum: d49f83c3580613966f71768ddb9a55a5
content_type: application/pdf
creator: dernst
date_created: 2022-02-21T08:45:11Z
date_updated: 2022-02-21T08:45:11Z
file_id: '10780'
file_name: 2022_PNAS_Slovakova.pdf
file_size: 1609678
relation: main_file
success: 1
file_date_updated: 2022-02-21T08:45:11Z
has_accepted_license: '1'
intvolume: ' 119'
isi: 1
issue: '8'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _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: 2521E28E-B435-11E9-9278-68D0E5697425
grant_number: 187-2013
name: Modulation of adhesion function in cell-cell contact formation by cortical
tension
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- '10916490'
publication_status: published
publisher: Proceedings of the National Academy of Sciences
quality_controlled: '1'
related_material:
record:
- id: '9750'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion
in zebrafish germ-layer progenitor cells
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 119
year: '2022'
...
---
_id: '10791'
abstract:
- lang: eng
text: The mammalian neocortex is composed of diverse neuronal and glial cell classes
that broadly arrange in six distinct laminae. Cortical layers emerge during development
and defects in the developmental programs that orchestrate cortical lamination
are associated with neurodevelopmental diseases. The developmental principle of
cortical layer formation depends on concerted radial projection neuron migration,
from their birthplace to their final target position. Radial migration occurs
in defined sequential steps, regulated by a large array of signaling pathways.
However, based on genetic loss-of-function experiments, most studies have thus
far focused on the role of cell-autonomous gene function. Yet, cortical neuron
migration in situ is a complex process and migrating neurons traverse along diverse
cellular compartments and environments. The role of tissue-wide properties and
genetic state in radial neuron migration is however not clear. Here we utilized
mosaic analysis with double markers (MADM) technology to either sparsely or globally
delete gene function, followed by quantitative single-cell phenotyping. The MADM-based
gene ablation paradigms in combination with computational modeling demonstrated
that global tissue-wide effects predominate cell-autonomous gene function albeit
in a gene-specific manner. Our results thus suggest that the genetic landscape
in a tissue critically affects the overall migration phenotype of individual cortical
projection neurons. In a broader context, our findings imply that global tissue-wide
effects represent an essential component of the underlying etiology associated
with focal malformations of cortical development in particular, and neurological
diseases in general.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
- _id: Bio
acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
Academy of Sciences. This work also received support from IST Austria institutional
funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC
funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical
support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer
lab for discussion. This research was supported by the Scientific Service Units
of IST Austria through resources provided by the Imaging and Optics Facility, Lab
Support Facility and Preclinical Facility."
article_number: kvac009
article_processing_charge: No
article_type: original
author:
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
- first_name: Li Huei
full_name: Tsai, Li Huei
last_name: Tsai
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic
gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1).
doi:10.1093/oons/kvac009
apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter,
S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration. Oxford Open Neuroscience. Oxford Academic.
https://doi.org/10.1093/oons/kvac009
chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena
Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override
Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience.
Oxford Academic, 2022. https://doi.org/10.1093/oons/kvac009.
ieee: A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration,” Oxford Open Neuroscience, vol. 1,
no. 1. Oxford Academic, 2022.
ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM,
Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects
override cell-intrinsic gene function in radial neuron migration. Oxford Open
Neuroscience. 1(1), kvac009.
mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function
in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009,
Oxford Academic, 2022, doi:10.1093/oons/kvac009.
short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter,
C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford
Open Neuroscience 1 (2022).
date_created: 2022-02-25T07:52:11Z
date_published: 2022-07-07T00:00:00Z
date_updated: 2023-11-30T10:55:12Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
- _id: BjHo
- _id: LifeSc
- _id: EM-Fac
doi: 10.1093/oons/kvac009
ec_funded: 1
file:
- access_level: open_access
checksum: 822e76e056c07099d1fb27d1ece5941b
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T08:00:30Z
date_updated: 2023-08-16T08:00:30Z
file_id: '14061'
file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf
file_size: 4846551
relation: main_file
success: 1
file_date_updated: 2023-08-16T08:00:30Z
has_accepted_license: '1'
intvolume: ' 1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
publication: Oxford Open Neuroscience
publication_identifier:
eissn:
- 2753-149X
publication_status: published
publisher: Oxford Academic
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
status: public
title: Tissue-wide effects override cell-intrinsic gene function in radial neuron
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2022'
...
---
_id: '11196'
abstract:
- lang: eng
text: "One of the fundamental questions in Neuroscience is how the structure of
synapses and their physiological properties are related. While synaptic transmission
remains a dynamic process, electron microscopy provides images with comparably
low temporal resolution (Studer et al., 2014). The current work overcomes this
challenge and describes an improved “Flash and Freeze” technique (Watanabe et
al., 2013a; Watanabe et al., 2013b) to study synaptic transmission at the hippocampal
mossy fiber-CA3 pyramidal neuron synapses, using mouse acute brain slices and
organotypic slices culture. The improved method allowed for selective stimulation
of presynaptic mossy fiber boutons and the observation of synaptic vesicle pool
dynamics at the active zones. Our results uncovered several intriguing morphological
features of mossy fiber boutons. First, the docked vesicle pool was largely depleted
(more than 70%) after stimulation, implying that the docked synaptic vesicles
pool and readily releasable pool are vastly overlapping in mossy fiber boutons.
Second, the synaptic vesicles are skewed towards larger diameters, displaying
a wide range of sizes. An increase in the mean diameter of synaptic vesicles,
after single and repetitive stimulation, suggests that smaller vesicles have a
higher release probability. Third, we observed putative endocytotic structures
after moderate light stimulation, matching the timing of previously described
ultrafast endocytosis (Watanabe et al., 2013a; Delvendahl et al., 2016). \r\n\tIn
addition, synaptic transmission depends on a sophisticated system of protein machinery
and calcium channels (Südhof, 2013b), which amplifies the challenge in studying
synaptic communication as these interactions can be potentially modified during
synaptic plasticity. And although recent study elucidated the potential correlation
between physiological and morphological properties of synapses during synaptic
plasticity (Vandael et al., 2020), the molecular underpinning of it remains unknown.
Thus, the presented work tries to overcome this challenge and aims to pinpoint
changes in the molecular architecture at hippocampal mossy fiber bouton synapses
during short- and long-term potentiation (STP and LTP), we combined chemical potentiation,
with the application of a cyclic adenosine monophosphate agonist (i.e. forskolin)
and freeze-fracture replica immunolabelling. This method allowed the localization
of membrane-bound proteins with nanometer precision within the active zone, in
particular, P/Q-type calcium channels and synaptic vesicle priming proteins Munc13-1/2.
First, we found that the number of clusters of Munc13-1 in the mossy fiber bouton
active zone increased significantly during STP, but decreased to lower than the
control value during LTP. Secondly, although the distance between the calcium
channels and Munc13-1s did not change after induction of STP, it shortened during
the LTP phase. Additionally, forskolin did not affect Munc13-2 distribution during
STP and LTP. These results indicate the existence of two distinct mechanisms that
govern STP and LTP at mossy fiber bouton synapses: an increase in the readily
realizable pool in the case of STP and a potential increase in release probability
during LTP. “Flash and freeze” and functional electron microscopy, are versatile
methods that can be successfully applied to intact brain circuits to study synaptic
transmission even at the molecular level.\r\n"
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
citation:
ama: Kim O. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses.
2022. doi:10.15479/at:ista:11196
apa: Kim, O. (2022). Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal
neuron synapses. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11196
chicago: Kim, Olena. “Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal
Neuron Synapses.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11196.
ieee: O. Kim, “Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron
synapses,” Institute of Science and Technology Austria, 2022.
ista: Kim O. 2022. Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron
synapses. Institute of Science and Technology Austria.
mla: Kim, Olena. Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron
Synapses. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11196.
short: O. Kim, Nanoarchitecture of Hippocampal Mossy Fiber-CA3 Pyramidal Neuron
Synapses, Institute of Science and Technology Austria, 2022.
date_created: 2022-04-20T09:47:12Z
date_published: 2022-04-20T00:00:00Z
date_updated: 2023-08-18T06:31:52Z
day: '20'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: PeJo
- _id: GradSch
doi: 10.15479/at:ista:11196
ec_funded: 1
file:
- access_level: open_access
checksum: 1616a8bf6f13a57c892dac873dcd0936
content_type: application/pdf
creator: okim
date_created: 2022-04-20T14:21:56Z
date_updated: 2023-04-20T22:30:03Z
embargo: 2023-04-19
file_id: '11220'
file_name: Olena_KIM_thesis_final.pdf
file_size: 21273537
relation: main_file
- access_level: closed
checksum: 1acb433f98dc42abb0b4b0cbb0c4b918
content_type: application/x-zip-compressed
creator: okim
date_created: 2022-04-20T14:22:56Z
date_updated: 2023-04-20T22:30:03Z
embargo_to: open_access
file_id: '11221'
file_name: KIM_thesis_final.zip
file_size: 59248569
relation: source_file
file_date_updated: 2023-04-20T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: '132'
project:
- _id: 25BAF7B2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '708497'
name: Presynaptic calcium channels distribution and impact on coupling at the hippocampal
mossy fiber synapse
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 25C3DBB6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01205
name: Zellkommunikation in Gesundheit und Krankheit
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '11222'
relation: part_of_dissertation
status: public
- id: '7473'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
title: Nanoarchitecture of hippocampal mossy fiber-CA3 pyramidal neuron synapses
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '11336'
abstract:
- lang: eng
text: The generation of a correctly-sized cerebral cortex with all-embracing neuronal
and glial cell-type diversity critically depends on faithful radial glial progenitor
(RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression
is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity
results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene
expression instructs RGP lineage progression is unknown. Here we utilize Mosaic
Analysis with Double Markers (MADM)-based single cell technology and demonstrate
that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts
at the global tissue-wide level. Conversely, cortical astrocyte production and
maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation.
We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression
that are dependent on complex interplays between intrinsic and tissue-wide properties.
In a broader context our results imply a critical role for the genetic and cellular
niche environment in neural stem cell behavior.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit) and S. Gharagozlou for technical support. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics
Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A.
received funding from the FWF Firnberg-Programm (T 1031). The work was supported by IST institutional funds and by the European Research Council (ERC) under the European Union’s Horizon
2020 research and innovation program (grant agreement 725780 LinPro) to S.H.
article_number: abq1263
article_processing_charge: No
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular
landscape shapes the execution of sequential PRC2 functions in neural stem cell
lineage progression. Science Advances. 2022;8(44). doi:10.1126/sciadv.abq1263
apa: Amberg, N., Pauler, F., Streicher, C., & Hippenmeyer, S. (2022). Tissue-wide
genetic and cellular landscape shapes the execution of sequential PRC2 functions
in neural stem cell lineage progression. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.abq1263
chicago: Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer.
“Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential
PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances.
American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abq1263.
ieee: N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression,” Science Advances, vol. 8, no. 44. American
Association for the Advancement of Science, 2022.
ista: Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression. Science Advances. 8(44), abq1263.
mla: Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the
Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.”
Science Advances, vol. 8, no. 44, abq1263, American Association for the
Advancement of Science, 2022, doi:10.1126/sciadv.abq1263.
short: N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).
date_created: 2022-04-26T15:04:50Z
date_published: 2022-11-01T00:00:00Z
date_updated: 2023-05-31T12:24:10Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.abq1263
ec_funded: 1
file:
- access_level: open_access
checksum: 0117023e188542082ca6693cf39e7f03
content_type: application/pdf
creator: patrickd
date_created: 2023-03-21T14:18:10Z
date_updated: 2023-03-21T14:18:10Z
file_id: '12742'
file_name: sciadv.abq1263.pdf
file_size: 2973998
relation: main_file
success: 1
file_date_updated: 2023-03-21T14:18:10Z
has_accepted_license: '1'
intvolume: ' 8'
issue: '44'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T0101031
name: Role of Eed in neural stem cell lineage progression
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/
scopus_import: '1'
status: public
title: Tissue-wide genetic and cellular landscape shapes the execution of sequential
PRC2 functions in neural stem cell lineage progression
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: 8
year: '2022'
...
---
_id: '11843'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein
located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids
involved in CD14 binding are highly conserved across pathogenic and non-pathogenic
strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration
by overactivation of integrins and blunted expression of co-stimulatory molecules
by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both
rate-limiting factors of T cell activation. This response was binary at the single-cell
level, but averaged in larger populations exposed to both piliated and non-piliated
pathogens, presumably via the exchange of immunomodulatory cytokines. While defining
an active molecular mechanism of immune evasion by pathogens, the interaction
between FimH and CD14 represents a potential target to interfere with persistent
and recurrent infections, such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89,
and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and
Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and
Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific
Service Units, especially the Bioimaging facility, the Preclinical facility and
the Electron microscopy facility for technical support, Jakob Wallner and all members
of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically
reading the manuscript. This work was supported by grants from the Austrian Research
Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373),
and the Austrian Science Fund (FWF P29911) to MS.
article_number: e78995
article_processing_charge: Yes
article_type: original
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- 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: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
eLife. 2022;11. doi:10.7554/eLife.78995
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. ELife. eLife Sciences Publications.
https://doi.org/10.7554/eLife.78995
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” ELife. eLife Sciences
Publications, 2022. https://doi.org/10.7554/eLife.78995.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type
1 piliated uropathogenic Escherichia coli hijack the host immune response by binding
to CD14. eLife. 11, e78995.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” ELife, vol. 11, e78995, eLife
Sciences Publications, 2022, doi:10.7554/eLife.78995.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
ELife 11 (2022).
date_created: 2022-08-14T22:01:46Z
date_published: 2022-07-26T00:00:00Z
date_updated: 2023-08-03T12:54:21Z
day: '26'
ddc:
- '570'
department:
- _id: MiSi
- _id: CaGu
doi: 10.7554/eLife.78995
ec_funded: 1
external_id:
isi:
- '000838410200001'
file:
- access_level: open_access
checksum: 002a3c7c7ea5caa9af9cfbea308f6ea4
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-16T08:57:37Z
date_updated: 2022-08-16T08:57:37Z
file_id: '11861'
file_name: 2022_eLife_Tomasek.pdf
file_size: 2057577
relation: main_file
success: 1
file_date_updated: 2022-08-16T08:57:37Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
record:
- id: '10316'
relation: earlier_version
status: public
scopus_import: '1'
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
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: 11
year: '2022'
...
---
_id: '11945'
abstract:
- lang: eng
text: "G protein-coupled receptors (GPCRs) respond to specific ligands and regulate
multiple processes ranging from cell growth and immune responses to neuronal signal
transmission. However, ligands for many GPCRs remain unknown, suffer from off-target
effects or have poor bioavailability. Additional challenges exist to dissect cell-type
specific responses when the same GPCR is expressed on several cell types within
the body. Here, we overcome these limitations by engineering DREADD-based GPCR
chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic
a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic
receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable
responses on second messenger and kinase activity, post-translational modifications,
and protein-protein interactions. Since β2AR is also enriched in microglia, which
can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR
in primary microglia and successfully recapitulate β2AR-mediated filopodia formation
through CNO stimulation. To dissect the role of selected GPCRs during microglial
inflammation, we additionally generated DREADD-based chimeras for microglia-enriched
GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65
both modulated the inflammatory response with a similar profile as endogenously
expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach
provides the means to obtain mechanistic and functional insights into GPCR signaling
on a cell-type specific level."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
citation:
ama: Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways
and modulate microglia function. 2022. doi:10.15479/at:ista:11945
apa: Schulz, R. (2022). Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function. Institute of Science and Technology
Austria. https://doi.org/10.15479/at:ista:11945
chicago: Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function.” Institute of Science and Technology
Austria, 2022. https://doi.org/10.15479/at:ista:11945.
ieee: R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function,” Institute of Science and Technology
Austria, 2022.
ista: Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling
pathways and modulate microglia function. Institute of Science and Technology
Austria.
mla: Schulz, Rouven. Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function. Institute of Science and Technology
Austria, 2022, doi:10.15479/at:ista:11945.
short: R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling
Pathways and Modulate Microglia Function, Institute of Science and Technology
Austria, 2022.
date_created: 2022-08-23T11:33:11Z
date_published: 2022-08-23T00:00:00Z
date_updated: 2023-08-03T13:02:26Z
day: '23'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/at:ista:11945
file:
- access_level: open_access
checksum: 61b1b666a210ff7cdd0e95ea75207a13
content_type: application/pdf
creator: rschulz
date_created: 2022-08-25T08:59:57Z
date_updated: 2022-08-25T08:59:57Z
file_id: '11970'
file_name: Thesis_Rouven_Schulz_2022_final.pdf
file_size: 28079331
relation: main_file
success: 1
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checksum: 2b8f95ea1c134dbdb927b41b1dbeeeb5
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: rschulz
date_created: 2022-08-25T09:00:11Z
date_updated: 2022-08-25T09:33:31Z
file_id: '11971'
file_name: Thesis_Rouven_Schulz_2022_final.docx
file_size: 27226963
relation: source_file
file_date_updated: 2022-08-25T09:33:31Z
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '133'
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '11995'
relation: dissertation_contains
status: public
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: Chimeric G protein-coupled receptors mimic distinct signaling pathways and
modulate microglia function
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: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '11995'
abstract:
- lang: eng
text: G protein-coupled receptors (GPCRs) regulate processes ranging from immune
responses to neuronal signaling. However, ligands for many GPCRs remain unknown,
suffer from off-target effects or have poor bioavailability. Additionally, dissecting
cell type-specific responses is challenging when the same GPCR is expressed on
different cells within a tissue. Here, we overcome these limitations by engineering
DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest.
We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second
messenger and kinase activity, post-translational modifications, and protein-protein
interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation
in microglia, an immune cell capable of driving central nervous system inflammation.
When dissecting microglial inflammation, we included two additional DREADD-based
chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65
modulate the inflammatory response with high similarity to endogenous β2AR, while
DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation
of cell type-dependent pathways without known endogenous ligands.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: The authors thank the Scientific Service Units at ISTA, in particular
the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility,
and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco
Benevento for sharing reagents and expertise. This research was supported by a DOC
Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences.
article_number: '4728'
article_processing_charge: No
article_type: original
author:
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Medina
full_name: Korkut, Medina
id: 4B51CE74-F248-11E8-B48F-1D18A9856A87
last_name: Korkut
orcid: 0000-0003-4309-2251
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic
distinct signaling pathways and modulate microglia responses. Nature Communications.
2022;13. doi:10.1038/s41467-022-32390-1
apa: Schulz, R., Korkut, M., Venturino, A., Colombo, G., & Siegert, S. (2022).
Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses.
Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32390-1
chicago: Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and
Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate
Microglia Responses.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32390-1.
ieee: R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric
GPCRs mimic distinct signaling pathways and modulate microglia responses,” Nature
Communications, vol. 13. Springer Nature, 2022.
ista: Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs
mimic distinct signaling pathways and modulate microglia responses. Nature Communications.
13, 4728.
mla: Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and
Modulate Microglia Responses.” Nature Communications, vol. 13, 4728, Springer
Nature, 2022, doi:10.1038/s41467-022-32390-1.
short: R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications
13 (2022).
date_created: 2022-08-28T22:01:59Z
date_published: 2022-08-15T00:00:00Z
date_updated: 2024-02-21T12:34:51Z
day: '15'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41467-022-32390-1
external_id:
isi:
- '000840984400032'
pmid:
- '35970889'
file:
- access_level: open_access
checksum: 191d9db0266e14a28d3a56dc7f65da84
content_type: application/pdf
creator: cchlebak
date_created: 2022-08-29T06:44:30Z
date_updated: 2022-08-29T06:44:30Z
file_id: '12002'
file_name: 2022_NatComm_Schulz.pdf
file_size: 7317396
relation: main_file
success: 1
file_date_updated: 2022-08-29T06:44:30Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 267F75D8-B435-11E9-9278-68D0E5697425
name: Modulating microglia through G protein-coupled receptor (GPCR) signaling
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/dreaddful-mimicry/
record:
- id: '11945'
relation: part_of_dissertation
status: public
- id: '11542'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses
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: '12244'
abstract:
- lang: eng
text: Environmental cues influence the highly dynamic morphology of microglia. Strategies
to characterize these changes usually involve user-selected morphometric features,
which preclude the identification of a spectrum of context-dependent morphological
phenotypes. Here we develop MorphOMICs, a topological data analysis approach,
which enables semiautomatic mapping of microglial morphology into an atlas of
cue-dependent phenotypes and overcomes feature-selection biases and biological
variability. We extract spatially heterogeneous and sexually dimorphic morphological
phenotypes for seven adult mouse brain regions. This sex-specific phenotype declines
with maturation but increases over the disease trajectories in two neurodegeneration
mouse models, with females showing a faster morphological shift in affected brain
regions. Remarkably, microglia morphologies reflect an adaptation upon repeated
exposure to ketamine anesthesia and do not recover to control morphologies. Finally,
we demonstrate that both long primary processes and short terminal processes provide
distinct insights to morphological phenotypes. MorphOMICs opens a new perspective
to characterize microglial morphology.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
acknowledgement: We thank the scientific service units at ISTA, in particular M. Schunn’s
team at the preclinical facility, and especially our colony manager S. Haslinger,
for excellent support. We are also grateful to the ISTA Imaging & Optics Facility,
and in particular C. Sommer for helping with the data file conversions. We thank
R. Erhart from the ISTA Scientific Computing Unit for improving the script performance.
We thank M. Maes, B. Nagy, S. Oakeley and M. Benevento and all members of the Siegert
group for constant feedback on the project and on the manuscript. This research
was supported by the European Union Horizon 2020 research and innovation program
under the Marie Skłodowska-Curie Actions program (754411 to R.J.A.C.), and by the
European Research Council (grant no. 715571 to S.S.). L.K. was supported by funding
to the Blue Brain Project, a research center of the École polytechnique fédérale
de Lausanne, from the Swiss government’s ETH Board of the Swiss Federal Institutes
of Technology. L.-H.T. was supported by NIH (grant no. R37NS051874) and by the JPB
Foundation. The funders had no role in study design, data collection and analysis,
decision to publish or preparation of the manuscript.
article_processing_charge: No
article_type: original
author:
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Lida
full_name: Kanari, Lida
last_name: Kanari
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Martina
full_name: Scolamiero, Martina
last_name: Scolamiero
- first_name: Jens
full_name: Agerberg, Jens
last_name: Agerberg
- first_name: Hansruedi
full_name: Mathys, Hansruedi
last_name: Mathys
- first_name: Li-Huei
full_name: Tsai, Li-Huei
last_name: Tsai
- first_name: Wojciech
full_name: Chachólski, Wojciech
last_name: Chachólski
- first_name: Kathryn
full_name: Hess, Kathryn
last_name: Hess
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Colombo G, Cubero RJ, Kanari L, et al. A tool for mapping microglial morphology,
morphOMICs, reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
2022;25(10):1379-1393. doi:10.1038/s41593-022-01167-6
apa: Colombo, G., Cubero, R. J., Kanari, L., Venturino, A., Schulz, R., Scolamiero,
M., … Siegert, S. (2022). A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes. Nature Neuroscience.
Springer Nature. https://doi.org/10.1038/s41593-022-01167-6
chicago: Colombo, Gloria, Ryan J Cubero, Lida Kanari, Alessandro Venturino, Rouven
Schulz, Martina Scolamiero, Jens Agerberg, et al. “A Tool for Mapping Microglial
Morphology, MorphOMICs, Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature
Neuroscience. Springer Nature, 2022. https://doi.org/10.1038/s41593-022-01167-6.
ieee: G. Colombo et al., “A tool for mapping microglial morphology, morphOMICs,
reveals brain-region and sex-dependent phenotypes,” Nature Neuroscience,
vol. 25, no. 10. Springer Nature, pp. 1379–1393, 2022.
ista: Colombo G, Cubero RJ, Kanari L, Venturino A, Schulz R, Scolamiero M, Agerberg
J, Mathys H, Tsai L-H, Chachólski W, Hess K, Siegert S. 2022. A tool for mapping
microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes.
Nature Neuroscience. 25(10), 1379–1393.
mla: Colombo, Gloria, et al. “A Tool for Mapping Microglial Morphology, MorphOMICs,
Reveals Brain-Region and Sex-Dependent Phenotypes.” Nature Neuroscience,
vol. 25, no. 10, Springer Nature, 2022, pp. 1379–93, doi:10.1038/s41593-022-01167-6.
short: G. Colombo, R.J. Cubero, L. Kanari, A. Venturino, R. Schulz, M. Scolamiero,
J. Agerberg, H. Mathys, L.-H. Tsai, W. Chachólski, K. Hess, S. Siegert, Nature
Neuroscience 25 (2022) 1379–1393.
date_created: 2023-01-16T09:53:07Z
date_published: 2022-10-01T00:00:00Z
date_updated: 2024-03-25T23:30:10Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1038/s41593-022-01167-6
ec_funded: 1
external_id:
isi:
- '000862214700001'
pmid:
- '36180790'
file:
- access_level: open_access
checksum: 28431146873096f52e0107b534f178c9
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T08:06:56Z
date_updated: 2023-01-30T08:06:56Z
file_id: '12437'
file_name: 2022_NatureNeuroscience_Colombo.pdf
file_size: 23789835
relation: main_file
success: 1
file_date_updated: 2023-01-30T08:06:56Z
has_accepted_license: '1'
intvolume: ' 25'
isi: 1
issue: '10'
keyword:
- General Neuroscience
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 1379-1393
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Nature Neuroscience
publication_identifier:
eissn:
- 1546-1726
issn:
- 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/morphomics-revealing-the-hidden-meaning-of-microglia-shape/
record:
- id: '12378'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A tool for mapping microglial morphology, morphOMICs, reveals brain-region
and sex-dependent phenotypes
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: 25
year: '2022'
...
---
_id: '12288'
abstract:
- lang: eng
text: To understand the function of neuronal circuits, it is crucial to disentangle
the connectivity patterns within the network. However, most tools currently used
to explore connectivity have low throughput, low selectivity, or limited accessibility.
Here, we report the development of an improved packaging system for the production
of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers
orders of magnitude higher with no background contamination, at a fraction of
the production time, while preserving the efficiency of transsynaptic labeling.
Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic
RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal
populations, tailored for diverse experimental requirements. We demonstrate the
power and flexibility of the new system by uncovering hidden local and distal
inhibitory connections in the mouse hippocampal formation and by imaging the functional
properties of a cortical microcircuit across weeks. Our novel production pipeline
provides a convenient approach to generate new rabies vectors, while our toolkit
flexibly and efficiently expands the current capacity to label, manipulate and
image the neuronal activity of interconnected neuronal circuits in vitro and in
vivo.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c
viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript.
This research was supported by the Scientific Service Units (SSU) of IST-Austria
through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical
Facility (PCF). This project was funded by the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation programme (ERC advanced
grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der
Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier
Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).
article_number: '79848'
article_processing_charge: No
article_type: original
author:
- first_name: Anton L
full_name: Sumser, Anton L
id: 3320A096-F248-11E8-B48F-1D18A9856A87
last_name: Sumser
orcid: 0000-0002-4792-1881
- first_name: Maximilian A
full_name: Jösch, Maximilian A
id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
last_name: Jösch
orcid: 0000-0002-3937-1330
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
citation:
ama: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production
of improved rabies viral vectors for specific, efficient and versatile transsynaptic
retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848
apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast,
high-throughput production of improved rabies viral vectors for specific, efficient
and versatile transsynaptic retrograde labeling. ELife. eLife Sciences
Publications. https://doi.org/10.7554/elife.79848
chicago: Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon.
“Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific,
Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife
Sciences Publications, 2022. https://doi.org/10.7554/elife.79848.
ieee: A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput
production of improved rabies viral vectors for specific, efficient and versatile
transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production
of improved rabies viral vectors for specific, efficient and versatile transsynaptic
retrograde labeling. eLife. 11, 79848.
mla: Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies
Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.”
ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848.
short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).
date_created: 2023-01-16T10:04:15Z
date_published: 2022-09-15T00:00:00Z
date_updated: 2023-08-04T10:29:48Z
day: '15'
ddc:
- '570'
department:
- _id: MaJö
- _id: PeJo
doi: 10.7554/elife.79848
ec_funded: 1
external_id:
isi:
- '000892204300001'
pmid:
- '36040301'
file:
- access_level: open_access
checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T11:50:53Z
date_updated: 2023-01-30T11:50:53Z
file_id: '12463'
file_name: 2022_eLife_Sumser.pdf
file_size: 8506811
relation: main_file
success: 1
file_date_updated: 2023-01-30T11:50:53Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '756502'
name: Circuits of Visual Attention
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: The Wittgenstein Prize
- _id: 266D407A-B435-11E9-9278-68D0E5697425
grant_number: LT000256
name: Neuronal networks of salience and spatial detection in the murine superior
colliculus
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1098-2017
name: Connecting sensory with motor processing in the superior colliculus
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Fast, high-throughput production of improved rabies viral vectors for specific,
efficient and versatile transsynaptic retrograde labeling
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: 11
year: '2022'
...
---
_id: '12378'
abstract:
- lang: eng
text: "Environmental cues influence the highly dynamic morphology of microglia.
Strategies to \r\ncharacterize these changes usually involve user-selected morphometric
features, which \r\npreclude the identification of a spectrum of context-dependent
morphological phenotypes. \r\nHere, we develop MorphOMICs, a topological data
analysis approach, which enables semi\x02automatic mapping of microglial morphology
into an atlas of cue-dependent phenotypes,\r\novercomes feature-selection bias
and minimizes biological variability. \r\nFirst, with MorphOMICs we derive the
morphological spectrum of microglia across seven \r\nbrain regions during postnatal
development and in two distinct Alzheimer’s disease \r\ndegeneration mouse models.
We uncover region-specific and sexually dimorphic\r\nmorphological trajectories,
with females showing an earlier morphological shift than males in \r\nthe degenerating
brain. Overall, we demonstrate that both long primary- and short terminal \r\nprocesses
provide distinct insights to morphological phenotypes. Moreover, using machine
\r\nlearning to map novel condition on the spectrum, we observe that microglia
morphologies \r\nreflect a dose-dependent adaptation upon ketamine anesthesia
and do not recover to control \r\nmorphologies.\r\nNext, we took advantage of
MorphOMICs to build a high-resolution and layer-specific map of \r\nmicroglial
morphological spectrum in the retina, covering postnatal development and rd10
\r\ndegeneration. Here, following photoreceptor death, microglia assume an early
development\x02like morphology. Finally, we map microglial morphology following
optic nerve crush on the \r\nretinal spectrum and observe a layer- and sex-dependent
response. \r\nOverall, MorphOMICs opens a new perspective to analyze microglial
morphology across \r\nmultiple conditions, and provides a novel tool to characterize
microglial morphology beyond \r\nthe traditionally dichotomized view of microglia."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
citation:
ama: Colombo G. MorphOMICs, a tool for mapping microglial morphology, reveals brain
region- and sex-dependent phenotypes. 2022. doi:10.15479/at:ista:12378
apa: Colombo, G. (2022). MorphOMICs, a tool for mapping microglial morphology,
reveals brain region- and sex-dependent phenotypes. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:12378
chicago: Colombo, Gloria. “MorphOMICs, a Tool for Mapping Microglial Morphology,
Reveals Brain Region- and Sex-Dependent Phenotypes.” Institute of Science and
Technology Austria, 2022. https://doi.org/10.15479/at:ista:12378.
ieee: G. Colombo, “MorphOMICs, a tool for mapping microglial morphology, reveals
brain region- and sex-dependent phenotypes,” Institute of Science and Technology
Austria, 2022.
ista: Colombo G. 2022. MorphOMICs, a tool for mapping microglial morphology, reveals
brain region- and sex-dependent phenotypes. Institute of Science and Technology
Austria.
mla: Colombo, Gloria. MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals
Brain Region- and Sex-Dependent Phenotypes. Institute of Science and Technology
Austria, 2022, doi:10.15479/at:ista:12378.
short: G. Colombo, MorphOMICs, a Tool for Mapping Microglial Morphology, Reveals
Brain Region- and Sex-Dependent Phenotypes, Institute of Science and Technology
Austria, 2022.
date_created: 2023-01-25T14:27:43Z
date_published: 2022-11-11T00:00:00Z
date_updated: 2023-08-04T09:40:37Z
day: '11'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SaSi
doi: 10.15479/at:ista:12378
ec_funded: 1
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content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
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date_updated: 2023-04-12T22:30:03Z
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file_id: '12379'
file_name: Gloria_Colombo_Thesis.docx
file_size: 23890382
relation: source_file
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content_type: application/pdf
creator: cchlebak
date_created: 2023-01-25T14:31:36Z
date_updated: 2023-04-12T22:30:03Z
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file_id: '12380'
file_name: Gloria_Colombo_Thesis.pdf
file_size: 13802421
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file_date_updated: 2023-04-12T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: '142'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '12244'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
title: MorphOMICs, a tool for mapping microglial morphology, reveals brain region-
and sex-dependent phenotypes
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: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '9794'
abstract:
- lang: eng
text: 'Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular
cells that form dedicated niches for immune cell interaction and capsular fibroblasts
that build a shell around the organ. Immunological challenge causes LNs to increase
more than tenfold in size within a few days. Here, we characterized the biomechanics
of LN swelling on the cellular and organ scale. We identified lymphocyte trapping
by influx and proliferation as drivers of an outward pressure force, causing fibroblastic
reticular cells of the T-zone (TRCs) and their associated conduits to stretch.
After an initial phase of relaxation, TRCs sensed the resulting strain through
cell matrix adhesions, which coordinated local growth and remodeling of the stromal
network. While the expanded TRC network readopted its typical configuration, a
massive fibrotic reaction of the organ capsule set in and countered further organ
expansion. Thus, different fibroblast populations mechanically control LN swelling
in a multitier fashion.'
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: PreCl
- _id: LifeSc
acknowledgement: This research was supported by the Scientific Service Units of IST
Austria through resources provided by the Imaging and Optics, Electron Microscopy,
Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd
antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing
a custom 3D channel alignment script. This work was supported by a European Research
Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR
20-24603Y and Charles University PRIMUS/20/MED/013.
article_processing_charge: No
article_type: original
author:
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Tommaso
full_name: Costanzo, Tommaso
id: D93824F4-D9BA-11E9-BB12-F207E6697425
last_name: Costanzo
orcid: 0000-0001-9732-3815
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Burkhard
full_name: Ludewig, Burkhard
last_name: Ludewig
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- 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: Wolfgang
full_name: Weninger, Wolfgang
last_name: Weninger
- 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: Sanjiv A.
full_name: Luther, Sanjiv A.
last_name: Luther
- first_name: Jens V.
full_name: Stein, Jens V.
last_name: Stein
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4
apa: Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W.,
… Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling
lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4
chicago: Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour,
Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal
Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature,
2022. https://doi.org/10.1038/s41590-022-01257-4.
ieee: F. P. Assen et al., “Multitier mechanics control stromal adaptations
in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature,
pp. 1246–1255, 2022.
ista: Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T,
Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo
EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 23, 1246–1255.
mla: Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in
Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022,
pp. 1246–55, doi:10.1038/s41590-022-01257-4.
short: F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T.
Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg,
W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology
23 (2022) 1246–1255.
date_created: 2021-08-06T09:09:11Z
date_published: 2022-07-11T00:00:00Z
date_updated: 2023-08-02T06:53:07Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
- _id: CaHe
- _id: EdHa
- _id: EM-Fac
- _id: Bio
- _id: MiSi
doi: 10.1038/s41590-022-01257-4
ec_funded: 1
external_id:
isi:
- '000822975900002'
file:
- access_level: open_access
checksum: 628e7b49809f22c75b428842efe70c68
content_type: application/pdf
creator: dernst
date_created: 2022-07-25T07:11:32Z
date_updated: 2022-07-25T07:11:32Z
file_id: '11642'
file_name: 2022_NatureImmunology_Assen.pdf
file_size: 11475325
relation: main_file
success: 1
file_date_updated: 2022-07-25T07:11:32Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1246-1255
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
publication: Nature Immunology
publication_identifier:
eissn:
- 1529-2916
issn:
- 1529-2908
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Multitier mechanics control stromal adaptations in swelling lymph nodes
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: 23
year: '2022'
...
---
_id: '9245'
abstract:
- lang: eng
text: Tissue morphogenesis is driven by mechanical forces triggering cell movements
and shape changes. Quantitatively measuring tension within tissues is of great
importance for understanding the role of mechanical signals acting on the cell
and tissue level during morphogenesis. Here we introduce laser ablation as a useful
tool to probe tissue tension within the granulosa layer, an epithelial monolayer
of somatic cells that surround the zebrafish female gamete during folliculogenesis.
We describe in detail how to isolate follicles, mount samples, perform laser surgery,
and analyze the data.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank Prof. Masazumi Tada and Roland Dosch for providing transgenic
zebrafish lines, the Heisenberg lab for technical assistance and feedback on the
manuscript, and the Bioimaging and Fish facilities of IST Austria for continuous
support. This work was funded by an ERC advanced grant (MECSPEC to C.-P.H.).
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
author:
- first_name: Peng
full_name: Xia, Peng
id: 4AB6C7D0-F248-11E8-B48F-1D18A9856A87
last_name: Xia
orcid: 0000-0002-5419-7756
- 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: 'Xia P, Heisenberg C-PJ. Quantifying tissue tension in the granulosa layer
after laser surgery. In: Dosch R, ed. Germline Development in the Zebrafish.
Vol 2218. Humana; 2021:117-128. doi:10.1007/978-1-0716-0970-5_10'
apa: Xia, P., & Heisenberg, C.-P. J. (2021). Quantifying tissue tension in the
granulosa layer after laser surgery. In R. Dosch (Ed.), Germline Development
in the Zebrafish (Vol. 2218, pp. 117–128). Humana. https://doi.org/10.1007/978-1-0716-0970-5_10
chicago: Xia, Peng, and Carl-Philipp J Heisenberg. “Quantifying Tissue Tension in
the Granulosa Layer after Laser Surgery.” In Germline Development in the Zebrafish,
edited by Roland Dosch, 2218:117–28. Humana, 2021. https://doi.org/10.1007/978-1-0716-0970-5_10.
ieee: P. Xia and C.-P. J. Heisenberg, “Quantifying tissue tension in the granulosa
layer after laser surgery,” in Germline Development in the Zebrafish, vol.
2218, R. Dosch, Ed. Humana, 2021, pp. 117–128.
ista: 'Xia P, Heisenberg C-PJ. 2021.Quantifying tissue tension in the granulosa
layer after laser surgery. In: Germline Development in the Zebrafish. Methods
in Molecular Biology, vol. 2218, 117–128.'
mla: Xia, Peng, and Carl-Philipp J. Heisenberg. “Quantifying Tissue Tension in the
Granulosa Layer after Laser Surgery.” Germline Development in the Zebrafish,
edited by Roland Dosch, vol. 2218, Humana, 2021, pp. 117–28, doi:10.1007/978-1-0716-0970-5_10.
short: P. Xia, C.-P.J. Heisenberg, in:, R. Dosch (Ed.), Germline Development in
the Zebrafish, Humana, 2021, pp. 117–128.
date_created: 2021-03-14T23:01:34Z
date_published: 2021-02-20T00:00:00Z
date_updated: 2022-06-03T10:57:55Z
day: '20'
department:
- _id: CaHe
doi: 10.1007/978-1-0716-0970-5_10
ec_funded: 1
editor:
- first_name: Roland
full_name: Dosch, Roland
last_name: Dosch
external_id:
pmid:
- '33606227'
intvolume: ' 2218'
keyword:
- Tissue tension
- Morphogenesis
- Laser ablation
- Zebrafish folliculogenesis
- Granulosa cells
language:
- iso: eng
month: '02'
oa_version: None
page: 117-128
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
publication: Germline Development in the Zebrafish
publication_identifier:
eisbn:
- 978-1-0716-0970-5
eissn:
- 1940-6029
isbn:
- 978-1-0716-0969-9
issn:
- 1064-3745
publication_status: published
publisher: Humana
quality_controlled: '1'
scopus_import: '1'
status: public
title: Quantifying tissue tension in the granulosa layer after laser surgery
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2218
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. Cell.
2021;184(7):1914-1928.e19. doi:10.1016/j.cell.2021.02.017
apa: Petridou, N., Corominas-Murtra, B., Heisenberg, C.-P. J., & Hannezo, E.
B. (2021). Rigidity percolation uncovers a structural basis for embryonic tissue
phase transitions. Cell. Elsevier. https://doi.org/10.1016/j.cell.2021.02.017
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.” Cell. Elsevier, 2021. https://doi.org/10.1016/j.cell.2021.02.017.
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,”
Cell, 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.” Cell, vol. 184, no. 7, Elsevier,
2021, p. 1914–1928.e19, doi:10.1016/j.cell.2021.02.017.
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: '9429'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
leads to motor coordination deficits as well as ASD-relevant social and cognitive
impairments. However, induction of Cul3 haploinsufficiency later in life does
not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
a critical developmental window. Here we show that Cul3 is essential to regulate
neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
display cortical lamination abnormalities. At the molecular level, we found that
Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
(Pls3), a previously unrecognized player of neural migration. Furthermore, we
found that Pls3 cell-autonomously regulates cell migration by regulating actin
cytoskeleton organization, and its levels are inversely proportional to neural
migration speed. Finally, we provide evidence that cellular phenotypes associated
with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
of the intact allele in vitro, offering a proof of concept for a potential therapeutic
approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
management of our animal colony, as well as M. Schunn and the Preclinical Facility
team for technical assistance. We thank K. Heesom and her team at the University
of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
(I3600-B27).
article_number: '3058'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-021-23123-x
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” Nature Communications,
vol. 12, no. 1. Springer Nature, 2021.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
a critical window of brain development. Nature Communications. 12(1), 3058.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” Nature Communications,
vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2024-09-10T12:04:26Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
isi:
- '000658769900010'
file:
- access_level: open_access
checksum: 337e0f7959c35ec959984cacdcb472ba
content_type: application/pdf
creator: kschuh
date_created: 2021-05-28T12:39:43Z
date_updated: 2021-05-28T12:39:43Z
file_id: '9430'
file_name: 2021_NatureCommunications_Morandell.pdf
file_size: 9358599
relation: main_file
success: 1
file_date_updated: 2021-05-28T12:39:43Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: Neural stem cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
record:
- id: '7800'
relation: earlier_version
status: public
- id: '12401'
relation: dissertation_contains
status: public
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain 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: 12
year: '2021'
...
---
_id: '9603'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) offers one approach to visualize
and concomitantly manipulate genetically defined cells in mice with single-cell
resolution. MADM applications include the analysis of lineage, single-cell morphology
and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous
gene functions in vivo in health and disease. Yet, MADM can only be applied to
<25% of all mouse genes on select chromosomes to date. To overcome this limitation,
we generate transgenic mice with knocked-in MADM cassettes near the centromeres
of all 19 autosomes and validate their use across organs. With this resource,
>96% of the entire mouse genome can now be subjected to single-cell genetic mosaic
analysis. Beyond a proof of principle, we apply our MADM library to systematically
trace sister chromatid segregation in distinct mitotic cell lineages. We find
striking chromosome-specific biases in segregation patterns, reflecting a putative
mechanism for the asymmetric segregation of genetic determinants in somatic stem
cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Bioimaging, Life Science, and Pre-Clinical Facilities
at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain,
M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance;
R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of
the Hippenmeyer lab for discussion. This work was supported by National Institutes
of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator
of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is
a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This
work also received support from IST Austria institutional funds , FWF SFB F78 to
S.H., the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme ( FP7/2007-2013 ) under REA grant agreement no 618444 to S.H.,
and the European Research Council (ERC) under the European Union’s Horizon 2020
Research and Innovation Programme (grant agreement no. 725780 LinPro ) to S.H.
article_number: '109274'
article_processing_charge: No
article_type: original
author:
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Amarbayasgalan
full_name: Davaatseren, Amarbayasgalan
id: 70ADC922-B424-11E9-99E3-BA18E6697425
last_name: Davaatseren
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Johanna
full_name: Sonntag, Johanna
id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87
last_name: Sonntag
- first_name: Lill
full_name: Andersen, Lill
last_name: Andersen
- first_name: Tina
full_name: Bernthaler, Tina
last_name: Bernthaler
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Randy L.
full_name: Johnson, Randy L.
last_name: Johnson
- first_name: Lindsay A.
full_name: Schwarz, Lindsay A.
last_name: Schwarz
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM
mice for single-cell genetic mosaic analysis. Cell Reports. 2021;35(12).
doi:10.1016/j.celrep.2021.109274
apa: Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen,
L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell
genetic mosaic analysis. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2021.109274
chicago: Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen,
Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library
of MADM Mice for Single-Cell Genetic Mosaic Analysis.” Cell Reports. Cell
Press, 2021. https://doi.org/10.1016/j.celrep.2021.109274.
ieee: X. Contreras et al., “A genome-wide library of MADM mice for single-cell
genetic mosaic analysis,” Cell Reports, vol. 35, no. 12. Cell Press, 2021.
ista: Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler
T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer
S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
Cell Reports. 35(12), 109274.
mla: Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell
Genetic Mosaic Analysis.” Cell Reports, vol. 35, no. 12, 109274, Cell Press,
2021, doi:10.1016/j.celrep.2021.109274.
short: X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen,
T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo,
T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).
date_created: 2021-06-27T22:01:48Z
date_published: 2021-06-22T00:00:00Z
date_updated: 2023-08-10T13:55:00Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
- _id: PreCl
doi: 10.1016/j.celrep.2021.109274
ec_funded: 1
external_id:
isi:
- '000664463600016'
file:
- access_level: open_access
checksum: d49520fdcbbb5c2f883bddb67cee5d77
content_type: application/pdf
creator: asandaue
date_created: 2021-06-28T14:06:24Z
date_updated: 2021-06-28T14:06:24Z
file_id: '9613'
file_name: 2021_CellReports_Contreras.pdf
file_size: 7653149
relation: main_file
success: 1
file_date_updated: 2021-06-28T14:06:24Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '12'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/
scopus_import: '1'
status: public
title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '9642'
abstract:
- lang: eng
text: Perineuronal nets (PNNs), components of the extracellular matrix, preferentially
coat parvalbumin-positive interneurons and constrain critical-period plasticity
in the adult cerebral cortex. Current strategies to remove PNN are long-lasting,
invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic
ketamine as a method with minimal behavioral effect. We find that this paradigm
strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like
plasticity. Microglia are critically involved in PNN loss because they engage
with parvalbumin-positive neurons in their defined cortical layer. We identify
external 60-Hz light-flickering entrainment to recapitulate microglia-mediated
PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques,
does not induce PNN loss, suggesting microglia might functionally tune to distinct
brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative
form of PNN intervention in the healthy adult brain.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank the scientific service units at IST Austria, especially
the IST bioimaging facility, the preclinical facility, and, specifically, Michael
Schunn and Sonja Haslinger for excellent support; Plexxikon for the PLX food; the
Csicsvari group for advice and equipment for in vivo recording; Jürgen Siegert for
the light-entrainment design; Marco Benevento, Soledad Gonzalo Cogno, Pat King,
and all Siegert group members for constant feedback on the project and manuscript;
Lorena Pantano (PILM Bioinformatics Core) for assisting with sample-size determination
for OD plasticity experiments; and Ana Morello from MIT for technical assistance
with VEPs recordings. This research was supported by a DOC Fellowship from the Austrian
Academy of Sciences at the Institute of Science and Technology Austria to R.S.,
from the European Union Horizon 2020 research and innovation program under the Marie
Skłodowska-Curie Actions program (grants 665385 to G.C.; 754411 to R.J.A.C.), the
European Research Council (grant 715571 to S.S.), and the National Eye Institute
of the National Institutes of Health under award numbers R01EY029245 (to M.F.B.)
and R01EY023037 (diversity supplement to H.D.J-C.).
article_number: '109313'
article_processing_charge: No
article_type: original
author:
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Rouven
full_name: Schulz, Rouven
id: 4C5E7B96-F248-11E8-B48F-1D18A9856A87
last_name: Schulz
orcid: 0000-0001-5297-733X
- first_name: Héctor
full_name: De Jesús-Cortés, Héctor
last_name: De Jesús-Cortés
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Balint
full_name: Nagy, Balint
id: 93C65ECC-A6F2-11E9-8DF9-9712E6697425
last_name: Nagy
- first_name: Francis
full_name: Reilly-Andújar, Francis
last_name: Reilly-Andújar
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Ryan J
full_name: Cubero, Ryan J
id: 850B2E12-9CD4-11E9-837F-E719E6697425
last_name: Cubero
orcid: 0000-0003-0002-1867
- first_name: Florianne E
full_name: Schoot Uiterkamp, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Schoot Uiterkamp
- first_name: Mark F.
full_name: Bear, Mark F.
last_name: Bear
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal
nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment
in the healthy brain. Cell Reports. 2021;36(1). doi:10.1016/j.celrep.2021.109313
apa: Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar,
F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly
upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.
Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109313
chicago: Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret
E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia
Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure
or 60-Hz Light Entrainment in the Healthy Brain.” Cell Reports. Elsevier,
2021. https://doi.org/10.1016/j.celrep.2021.109313.
ieee: A. Venturino et al., “Microglia enable mature perineuronal nets disassembly
upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,”
Cell Reports, vol. 36, no. 1. Elsevier, 2021.
ista: Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar
F, Colombo G, Cubero RJ, Schoot Uiterkamp FE, Bear MF, Siegert S. 2021. Microglia
enable mature perineuronal nets disassembly upon anesthetic ketamine exposure
or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313.
mla: Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly
upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.”
Cell Reports, vol. 36, no. 1, 109313, Elsevier, 2021, doi:10.1016/j.celrep.2021.109313.
short: A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar,
G. Colombo, R.J. Cubero, F.E. Schoot Uiterkamp, M.F. Bear, S. Siegert, Cell Reports
36 (2021).
date_created: 2021-07-11T22:01:16Z
date_published: 2021-07-06T00:00:00Z
date_updated: 2023-08-10T14:09:39Z
day: '06'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1016/j.celrep.2021.109313
ec_funded: 1
external_id:
isi:
- '000670188500004'
pmid:
- '34233180'
file:
- access_level: open_access
checksum: f056255f6d01fd9a86b5387635928173
content_type: application/pdf
creator: cziletti
date_created: 2021-07-19T13:32:17Z
date_updated: 2021-07-19T13:32:17Z
file_id: '9693'
file_name: 2021_CellReports_Venturino.pdf
file_size: 56388540
relation: main_file
success: 1
file_date_updated: 2021-07-19T13:32:17Z
has_accepted_license: '1'
intvolume: ' 36'
isi: 1
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Cell Reports
publication_identifier:
eissn:
- '22111247'
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/the-twinkle-and-the-brain/
scopus_import: '1'
status: public
title: Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine
exposure or 60-Hz light entrainment in the healthy brain
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: 36
year: '2021'
...
---
_id: '10146'
abstract:
- lang: eng
text: The enzymes of the mitochondrial electron transport chain are key players
of cell metabolism. Despite being active when isolated, in vivo they associate
into supercomplexes1, whose precise role is debated. Supercomplexes CIII2CIV1-2
(refs. 2,3), CICIII2 (ref. 4) and CICIII2CIV (respirasome)5,6,7,8,9,10 exist in
mammals, but in contrast to CICIII2 and the respirasome, to date the only known
eukaryotic structures of CIII2CIV1-2 come from Saccharomyces cerevisiae11,12 and
plants13, which have different organization. Here we present the first, to our
knowledge, structures of mammalian (mouse and ovine) CIII2CIV and its assembly
intermediates, in different conformations. We describe the assembly of CIII2CIV
from the CIII2 precursor to the final CIII2CIV conformation, driven by the insertion
of the N terminus of the assembly factor SCAF1 (ref. 14) deep into CIII2, while
its C terminus is integrated into CIV. Our structures (which include CICIII2 and
the respirasome) also confirm that SCAF1 is exclusively required for the assembly
of CIII2CIV and has no role in the assembly of the respirasome. We show that CIII2
is asymmetric due to the presence of only one copy of subunit 9, which straddles
both monomers and prevents the attachment of a second copy of SCAF1 to CIII2,
explaining the presence of one copy of CIV in CIII2CIV in mammals. Finally, we
show that CIII2 and CIV gain catalytic advantage when assembled into the supercomplex
and propose a role for CIII2CIV in fine tuning the efficiency of electron transfer
in the electron transport chain.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: ScienComp
acknowledgement: We thank the pre-clinical facility of the IST Austria and A. Venturino
for assistance with the animals; and V.-V. Hodirnau for assistance during the Titan
Krios data collection, performed at the IST Austria. The data processing was performed
at the IST high-performance computing cluster. This project has received funding
from the European Union’s Horizon 2020 research and innovation program under the
Marie Skłodowska-Curie grant agreement no. 754411.
article_processing_charge: No
article_type: original
author:
- first_name: Irene
full_name: Vercellino, Irene
id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
last_name: Vercellino
orcid: 0000-0001-5618-3449
- first_name: Leonid A
full_name: Sazanov, Leonid A
id: 338D39FE-F248-11E8-B48F-1D18A9856A87
last_name: Sazanov
orcid: 0000-0002-0977-7989
citation:
ama: Vercellino I, Sazanov LA. Structure and assembly of the mammalian mitochondrial
supercomplex CIII2CIV. Nature. 2021;598(7880):364-367. doi:10.1038/s41586-021-03927-z
apa: Vercellino, I., & Sazanov, L. A. (2021). Structure and assembly of the
mammalian mitochondrial supercomplex CIII2CIV. Nature. Springer
Nature. https://doi.org/10.1038/s41586-021-03927-z
chicago: Vercellino, Irene, and Leonid A Sazanov. “Structure and Assembly of the
Mammalian Mitochondrial Supercomplex CIII2CIV.” Nature. Springer
Nature, 2021. https://doi.org/10.1038/s41586-021-03927-z.
ieee: I. Vercellino and L. A. Sazanov, “Structure and assembly of the mammalian
mitochondrial supercomplex CIII2CIV,” Nature, vol. 598, no.
7880. Springer Nature, pp. 364–367, 2021.
ista: Vercellino I, Sazanov LA. 2021. Structure and assembly of the mammalian mitochondrial
supercomplex CIII2CIV. Nature. 598(7880), 364–367.
mla: Vercellino, Irene, and Leonid A. Sazanov. “Structure and Assembly of the Mammalian
Mitochondrial Supercomplex CIII2CIV.” Nature, vol. 598, no.
7880, Springer Nature, 2021, pp. 364–67, doi:10.1038/s41586-021-03927-z.
short: I. Vercellino, L.A. Sazanov, Nature 598 (2021) 364–367.
date_created: 2021-10-17T22:01:17Z
date_published: 2021-10-14T00:00:00Z
date_updated: 2023-08-14T08:01:21Z
day: '14'
department:
- _id: LeSa
doi: 10.1038/s41586-021-03927-z
ec_funded: 1
external_id:
isi:
- '000704581600001'
pmid:
- '34616041'
intvolume: ' 598'
isi: 1
issue: '7880'
language:
- iso: eng
month: '10'
oa_version: None
page: 364-367
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
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/boosting-the-cells-power-house/
scopus_import: '1'
status: public
title: Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 598
year: '2021'
...
---
_id: '10307'
abstract:
- lang: eng
text: Bacteria-host interactions represent a continuous trade-off between benefit
and risk. Thus, the host immune response is faced with a non-trivial problem –
accommodate beneficial commensals and remove harmful pathogens. This is especially
difficult as molecular patterns, such as lipopolysaccharide or specific surface
organelles such as pili, are conserved in both, commensal and pathogenic bacteria.
Type 1 pili, tightly regulated by phase variation, are considered an important
virulence factor of pathogenic bacteria as they facilitate invasion into host
cells. While invasion represents a de facto passive mechanism for pathogens to
escape the host immune response, we demonstrate a fundamental role of type 1 pili
as active modulators of the innate and adaptive immune response.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
- _id: PreCl
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
citation:
ama: Tomasek K. Pathogenic Escherichia coli hijack the host immune response. 2021.
doi:10.15479/at:ista:10307
apa: Tomasek, K. (2021). Pathogenic Escherichia coli hijack the host immune response.
Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:10307
chicago: Tomasek, Kathrin. “Pathogenic Escherichia Coli Hijack the Host Immune Response.”
Institute of Science and Technology Austria, 2021. https://doi.org/10.15479/at:ista:10307.
ieee: K. Tomasek, “Pathogenic Escherichia coli hijack the host immune response,”
Institute of Science and Technology Austria, 2021.
ista: Tomasek K. 2021. Pathogenic Escherichia coli hijack the host immune response.
Institute of Science and Technology Austria.
mla: Tomasek, Kathrin. Pathogenic Escherichia Coli Hijack the Host Immune Response.
Institute of Science and Technology Austria, 2021, doi:10.15479/at:ista:10307.
short: K. Tomasek, Pathogenic Escherichia Coli Hijack the Host Immune Response,
Institute of Science and Technology Austria, 2021.
date_created: 2021-11-18T15:05:06Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2023-09-07T13:34:38Z
day: '18'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
- _id: CaGu
- _id: GradSch
doi: 10.15479/at:ista:10307
file:
- access_level: open_access
checksum: b39c9e0ef18d0484d537a67551effd02
content_type: application/pdf
creator: ktomasek
date_created: 2021-11-18T15:07:31Z
date_updated: 2022-12-20T23:30:05Z
embargo: 2022-11-18
file_id: '10308'
file_name: ThesisTomasekKathrin.pdf
file_size: 13266088
relation: main_file
- access_level: closed
checksum: c0c440ee9e5ef1102a518a4f9f023e7c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: ktomasek
date_created: 2021-11-18T15:07:46Z
date_updated: 2022-12-20T23:30:05Z
embargo_to: open_access
file_id: '10309'
file_name: ThesisTomasekKathrin.docx
file_size: 7539509
relation: source_file
file_date_updated: 2022-12-20T23:30:05Z
has_accepted_license: '1'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: '73'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '10316'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
title: Pathogenic Escherichia coli hijack the host immune response
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2021'
...
---
_id: '10316'
abstract:
- lang: eng
text: A key attribute of persistent or recurring bacterial infections is the ability
of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express
type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and
establish persistent infections. However, the molecular mechanisms and strategies
by which bacteria actively circumvent the immune response of the host remain poorly
understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide
detection, on dendritic cells as a previously undescribed binding partner of FimH,
the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH
amino acids involved in CD14 binding are highly conserved across pathogenic and
non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced
dendritic cell migration and blunted expression of co-stimulatory molecules, both
rate-limiting factors of T cell activation. While defining an active molecular
mechanism of immune evasion by pathogens, the interaction between FimH and CD14
represents a potential target to interfere with persistent and recurrent infections,
such as urinary tract infections or Crohn’s disease.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra
and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments
and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis.
We thank the IST Austria Scientific Service Units, especially the Bioimaging facility,
the Preclinical facility and the Electron microscopy facility for technical support,
Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions
and Daria Siekhaus for critically reading the manuscript. This work was supported
by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G.,
the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911)
to M.S.
article_processing_charge: No
author:
- first_name: Kathrin
full_name: Tomasek, Kathrin
id: 3AEC8556-F248-11E8-B48F-1D18A9856A87
last_name: Tomasek
orcid: 0000-0003-3768-877X
- first_name: Alexander F
full_name: Leithner, Alexander F
id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
last_name: Leithner
orcid: 0000-0002-1073-744X
- first_name: Ivana
full_name: Glatzová, Ivana
id: 727b3c7d-4939-11ec-89b3-b9b0750ab74d
last_name: Glatzová
- first_name: Michael S.
full_name: Lukesch, Michael S.
last_name: Lukesch
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv. doi:10.1101/2021.10.18.464770
apa: Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &
Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the
host immune response by binding to CD14. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2021.10.18.464770
chicago: Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch,
Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli
Hijack the Host Immune Response by Binding to CD14.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2021.10.18.464770.
ieee: K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M.
K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune
response by binding to CD14,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated
uropathogenic Escherichia coli hijack the host immune response by binding to CD14.
bioRxiv, 10.1101/2021.10.18.464770.
mla: Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack
the Host Immune Response by Binding to CD14.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/2021.10.18.464770.
short: K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt,
BioRxiv (n.d.).
date_created: 2021-11-19T12:24:16Z
date_published: 2021-10-18T00:00:00Z
date_updated: 2024-03-25T23:30:19Z
day: '18'
department:
- _id: CaGu
- _id: MiSi
doi: 10.1101/2021.10.18.464770
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '11843'
relation: later_version
status: public
- id: '10307'
relation: dissertation_contains
status: public
status: public
title: Type 1 piliated uropathogenic Escherichia coli hijack the host immune response
by binding to CD14
type: preprint
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2021'
...