---
_id: '9629'
abstract:
- lang: eng
text: Intestinal organoids derived from single cells undergo complex crypt–villus
patterning and morphogenesis. However, the nature and coordination of the underlying
forces remains poorly characterized. Here, using light-sheet microscopy and large-scale
imaging quantification, we demonstrate that crypt formation coincides with a stark
reduction in lumen volume. We develop a 3D biophysical model to computationally
screen different mechanical scenarios of crypt morphogenesis. Combining this with
live-imaging data and multiple mechanical perturbations, we show that actomyosin-driven
crypt apical contraction and villus basal tension work synergistically with lumen
volume reduction to drive crypt morphogenesis, and demonstrate the existence of
a critical point in differential tensions above which crypt morphology becomes
robust to volume changes. Finally, we identified a sodium/glucose cotransporter
that is specific to differentiated enterocytes that modulates lumen volume reduction
through cell swelling in the villus region. Together, our study uncovers the cellular
basis of how cell fate modulates osmotic and actomyosin forces to coordinate robust
morphogenesis.
acknowledgement: 'We acknowledge the members of the Lennon-Duménil laboratory for
sharing the mouse line of Myh9-GFP. We are grateful to the members of the Liberali
laboratory and the FMI facilities for their support. We thank E. Tagliavini for
IT support; L. Gelman for assistance and training; S. Bichet and A. Bogucki for
helping with histology of mouse tissues; H. Kohler for fluorescence-activated cell
sorting; G. Q. G. de Medeiros for maintenance of light-sheet microscopy; M. G. Stadler
for scRNA-seq analysis; G. Gay for discussions on the 3D vertex model; the members
of the Liberali laboratory, C. P. Heisenberg and C. Tsiairis for reading and providing
feedback on the manuscript. Funding: Q.Y. is supported by a Postdoc fellowship from
Peter und Taul Engelhorn Stiftung (PTES). This work received funding from the European
Research Council (ERC) under the EU Horizon 2020 research and Innovation Programme
Grant Agreement no. 758617 (to P.L.), the Swiss National Foundation (SNF) (POOP3_157531,
to P.L.) and from the ERC under the EU Horizon 2020 Research and Innovation Program
Grant Agreements 851288 (to E.H.) and the Austrian Science Fund (FWF) (P31639, to
E.H.).'
article_processing_charge: No
article_type: original
author:
- first_name: Qiutan
full_name: Yang, Qiutan
last_name: Yang
- first_name: Shi-lei
full_name: Xue, Shi-lei
id: 31D2C804-F248-11E8-B48F-1D18A9856A87
last_name: Xue
- first_name: Chii Jou
full_name: Chan, Chii Jou
last_name: Chan
- first_name: Markus
full_name: Rempfler, Markus
last_name: Rempfler
- first_name: Dario
full_name: Vischi, Dario
last_name: Vischi
- first_name: Francisca
full_name: Maurer-Gutierrez, Francisca
last_name: Maurer-Gutierrez
- first_name: Takashi
full_name: Hiiragi, Takashi
last_name: Hiiragi
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Prisca
full_name: Liberali, Prisca
last_name: Liberali
citation:
ama: Yang Q, Xue S, Chan CJ, et al. Cell fate coordinates mechano-osmotic forces
in intestinal crypt formation. Nature Cell Biology. 2021;23:733–744. doi:10.1038/s41556-021-00700-2
apa: Yang, Q., Xue, S., Chan, C. J., Rempfler, M., Vischi, D., Maurer-Gutierrez,
F., … Liberali, P. (2021). Cell fate coordinates mechano-osmotic forces in intestinal
crypt formation. Nature Cell Biology. Springer Nature. https://doi.org/10.1038/s41556-021-00700-2
chicago: Yang, Qiutan, Shi-lei Xue, Chii Jou Chan, Markus Rempfler, Dario Vischi,
Francisca Maurer-Gutierrez, Takashi Hiiragi, Edouard B Hannezo, and Prisca Liberali.
“Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal Crypt Formation.”
Nature Cell Biology. Springer Nature, 2021. https://doi.org/10.1038/s41556-021-00700-2.
ieee: Q. Yang et al., “Cell fate coordinates mechano-osmotic forces in intestinal
crypt formation,” Nature Cell Biology, vol. 23. Springer Nature, pp. 733–744,
2021.
ista: Yang Q, Xue S, Chan CJ, Rempfler M, Vischi D, Maurer-Gutierrez F, Hiiragi
T, Hannezo EB, Liberali P. 2021. Cell fate coordinates mechano-osmotic forces
in intestinal crypt formation. Nature Cell Biology. 23, 733–744.
mla: Yang, Qiutan, et al. “Cell Fate Coordinates Mechano-Osmotic Forces in Intestinal
Crypt Formation.” Nature Cell Biology, vol. 23, Springer Nature, 2021,
pp. 733–744, doi:10.1038/s41556-021-00700-2.
short: Q. Yang, S. Xue, C.J. Chan, M. Rempfler, D. Vischi, F. Maurer-Gutierrez,
T. Hiiragi, E.B. Hannezo, P. Liberali, Nature Cell Biology 23 (2021) 733–744.
date_created: 2021-07-04T22:01:25Z
date_published: 2021-06-21T00:00:00Z
date_updated: 2023-08-10T13:57:36Z
day: '21'
department:
- _id: EdHa
doi: 10.1038/s41556-021-00700-2
ec_funded: 1
external_id:
isi:
- '000664016300003'
pmid:
- '34155381'
intvolume: ' 23'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.biorxiv.org/content/10.1101/2020.05.13.094359
month: '06'
oa: 1
oa_version: Preprint
page: 733–744
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 268294B6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31639
name: Active mechano-chemical description of the cell cytoskeleton
publication: Nature Cell Biology
publication_identifier:
eissn:
- 1476-4679
issn:
- 1465-7392
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cell fate coordinates mechano-osmotic forces in intestinal crypt formation
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 23
year: '2021'
...
---
_id: '10365'
abstract:
- lang: eng
text: The early development of many organisms involves the folding of cell monolayers,
but this behaviour is difficult to reproduce in vitro; therefore, both mechanistic
causes and effects of local curvature remain unclear. Here we study epithelial
cell monolayers on corrugated hydrogels engineered into wavy patterns, examining
how concave and convex curvatures affect cellular and nuclear shape. We find that
substrate curvature affects monolayer thickness, which is larger in valleys than
crests. We show that this feature generically arises in a vertex model, leading
to the hypothesis that cells may sense curvature by modifying the thickness of
the tissue. We find that local curvature also affects nuclear morphology and positioning,
which we explain by extending the vertex model to take into account membrane–nucleus
interactions, encoding thickness modulation in changes to nuclear deformation
and position. We propose that curvature governs the spatial distribution of yes-associated
proteins via nuclear shape and density changes. We show that curvature also induces
significant variations in lamins, chromatin condensation and cell proliferation
rate in folded epithelial tissues. Together, this work identifies active cell
mechanics and nuclear mechanoadaptation as the key players of the mechanistic
regulation of epithelia to substrate curvature.
acknowledgement: S.G. acknowledges funding from FEDER Prostem Research Project no.
1510614 (Wallonia DG06), F.R.S.-FNRS Epiforce Research Project no. T.0092.21 and
Interreg MAT(T)ISSE project, which is financially supported by Interreg France-Wallonie-Vlaanderen
(Fonds Européen de Développement Régional, FEDER-ERDF). This project was supported
by the European Research Council under the European Union’s Horizon 2020 Research
and Innovation Programme grant agreement 851288 (to E.H.), and by the Austrian Science
Fund (FWF) (P 31639; to E.H.). L.R.M. acknowledges funding from the Agence National
de la Recherche (ANR), as part of the ‘Investments d’Avenir’ Programme (I-SITE ULNE/ANR-16-IDEX-0004
ULNE). This work benefited from ANR-10-EQPX-04-01 and FEDER 12001407 grants to F.L.
W.D.V. is supported by the Research Foundation Flanders (FWO 1516619N, FWO GOO5819N,
FWO I003420N, FWO IRI I000321N) and is member of the Research Excellence Consortium
µNEURO at the University of Antwerp. M.L. is financially supported by FRIA (F.R.S.-FNRS).
M.S. is a Senior Research Associate of the Fund for Scientific Research (F.R.S.-FNRS)
and acknowledges EOS grant no. 30650939 (PRECISION). Sketches in Figs. 1a and 5e
and Extended Data Fig. 9 were drawn by C. Levicek.
article_processing_charge: No
article_type: original
author:
- first_name: Marine
full_name: Luciano, Marine
last_name: Luciano
- first_name: Shi-lei
full_name: Xue, Shi-lei
id: 31D2C804-F248-11E8-B48F-1D18A9856A87
last_name: Xue
- first_name: Winnok H.
full_name: De Vos, Winnok H.
last_name: De Vos
- first_name: Lorena
full_name: Redondo-Morata, Lorena
last_name: Redondo-Morata
- first_name: Mathieu
full_name: Surin, Mathieu
last_name: Surin
- first_name: Frank
full_name: Lafont, Frank
last_name: Lafont
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Sylvain
full_name: Gabriele, Sylvain
last_name: Gabriele
citation:
ama: Luciano M, Xue S, De Vos WH, et al. Cell monolayers sense curvature by exploiting
active mechanics and nuclear mechanoadaptation. Nature Physics. 2021;17(12):1382–1390.
doi:10.1038/s41567-021-01374-1
apa: Luciano, M., Xue, S., De Vos, W. H., Redondo-Morata, L., Surin, M., Lafont,
F., … Gabriele, S. (2021). Cell monolayers sense curvature by exploiting active
mechanics and nuclear mechanoadaptation. Nature Physics. Springer Nature.
https://doi.org/10.1038/s41567-021-01374-1
chicago: Luciano, Marine, Shi-lei Xue, Winnok H. De Vos, Lorena Redondo-Morata,
Mathieu Surin, Frank Lafont, Edouard B Hannezo, and Sylvain Gabriele. “Cell Monolayers
Sense Curvature by Exploiting Active Mechanics and Nuclear Mechanoadaptation.”
Nature Physics. Springer Nature, 2021. https://doi.org/10.1038/s41567-021-01374-1.
ieee: M. Luciano et al., “Cell monolayers sense curvature by exploiting active
mechanics and nuclear mechanoadaptation,” Nature Physics, vol. 17, no.
12. Springer Nature, pp. 1382–1390, 2021.
ista: Luciano M, Xue S, De Vos WH, Redondo-Morata L, Surin M, Lafont F, Hannezo
EB, Gabriele S. 2021. Cell monolayers sense curvature by exploiting active mechanics
and nuclear mechanoadaptation. Nature Physics. 17(12), 1382–1390.
mla: Luciano, Marine, et al. “Cell Monolayers Sense Curvature by Exploiting Active
Mechanics and Nuclear Mechanoadaptation.” Nature Physics, vol. 17, no.
12, Springer Nature, 2021, pp. 1382–1390, doi:10.1038/s41567-021-01374-1.
short: M. Luciano, S. Xue, W.H. De Vos, L. Redondo-Morata, M. Surin, F. Lafont,
E.B. Hannezo, S. Gabriele, Nature Physics 17 (2021) 1382–1390.
date_created: 2021-11-28T23:01:29Z
date_published: 2021-11-18T00:00:00Z
date_updated: 2023-10-16T06:31:54Z
day: '18'
ddc:
- '530'
department:
- _id: EdHa
doi: 10.1038/s41567-021-01374-1
ec_funded: 1
external_id:
isi:
- '000720204300004'
file:
- access_level: open_access
checksum: 5d6d76750a71d7cb632bb15417c38ef7
content_type: application/pdf
creator: channezo
date_created: 2023-10-11T09:31:43Z
date_updated: 2023-10-11T09:31:43Z
file_id: '14420'
file_name: 50145_4_merged_1630498627.pdf
file_size: 40285498
relation: main_file
success: 1
file_date_updated: 2023-10-11T09:31:43Z
has_accepted_license: '1'
intvolume: ' 17'
isi: 1
issue: '12'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: 1382–1390
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 268294B6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31639
name: Active mechano-chemical description of the cell cytoskeleton
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Webpage
relation: press_release
url: https://ist.ac.at/en/news/how-cells-feel-curvature/
scopus_import: '1'
status: public
title: Cell monolayers sense curvature by exploiting active mechanics and nuclear
mechanoadaptation
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2021'
...
---
_id: '6508'
abstract:
- lang: eng
text: Segregation of maternal determinants within the oocyte constitutes the first
step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming
leads to the segregation of ooplasm from yolk granules along the animal-vegetal
axis of the oocyte. Here, we show that this process does not rely on cortical
actin reorganization, as previously thought, but instead on a cell-cycle-dependent
bulk actin polymerization wave traveling from the animal to the vegetal pole of
the oocyte. This wave functions in segregation by both pulling ooplasm animally
and pushing yolk granules vegetally. Using biophysical experimentation and theory,
we show that ooplasm pulling is mediated by bulk actin network flows exerting
friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism
closely resembling actin comet formation on yolk granules. Our study defines a
novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte
polarization via ooplasmic segregation.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We would like to thank Pierre Recho, Guillaume Salbreux, and Silvia
Grigolon for advice on the theory, Lila Solnica-Krezel for kindly providing us with
zebrafish dachsous mutants, members of the Heisenberg and Hannezo groups for fruitful
discussions, and the Bioimaging and zebrafish facilities at IST Austria for their
continuous support. This project has received funding from the European Union (European
Research Council Advanced Grant 742573 to C.P.H.) and from the Austrian Science
Fund (FWF) (P 31639 to E.H.).
article_processing_charge: No
article_type: original
author:
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Roland
full_name: Kardos, Roland
id: 4039350E-F248-11E8-B48F-1D18A9856A87
last_name: Kardos
- first_name: Shi-lei
full_name: Xue, Shi-lei
id: 31D2C804-F248-11E8-B48F-1D18A9856A87
last_name: Xue
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
citation:
ama: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. Bulk actin
dynamics drive phase segregation in zebrafish oocytes. Cell. 2019;177(6):1463-1479.e18.
doi:10.1016/j.cell.2019.04.030
apa: Shamipour, S., Kardos, R., Xue, S., Hof, B., Hannezo, E. B., & Heisenberg,
C.-P. J. (2019). Bulk actin dynamics drive phase segregation in zebrafish oocytes.
Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.04.030
chicago: Shamipour, Shayan, Roland Kardos, Shi-lei Xue, Björn Hof, Edouard B Hannezo,
and Carl-Philipp J Heisenberg. “Bulk Actin Dynamics Drive Phase Segregation in
Zebrafish Oocytes.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.04.030.
ieee: S. Shamipour, R. Kardos, S. Xue, B. Hof, E. B. Hannezo, and C.-P. J. Heisenberg,
“Bulk actin dynamics drive phase segregation in zebrafish oocytes,” Cell,
vol. 177, no. 6. Elsevier, p. 1463–1479.e18, 2019.
ista: Shamipour S, Kardos R, Xue S, Hof B, Hannezo EB, Heisenberg C-PJ. 2019. Bulk
actin dynamics drive phase segregation in zebrafish oocytes. Cell. 177(6), 1463–1479.e18.
mla: Shamipour, Shayan, et al. “Bulk Actin Dynamics Drive Phase Segregation in Zebrafish
Oocytes.” Cell, vol. 177, no. 6, Elsevier, 2019, p. 1463–1479.e18, doi:10.1016/j.cell.2019.04.030.
short: S. Shamipour, R. Kardos, S. Xue, B. Hof, E.B. Hannezo, C.-P.J. Heisenberg,
Cell 177 (2019) 1463–1479.e18.
date_created: 2019-06-02T21:59:12Z
date_published: 2019-05-30T00:00:00Z
date_updated: 2024-03-28T23:30:39Z
day: '30'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
- _id: BjHo
doi: 10.1016/j.cell.2019.04.030
ec_funded: 1
external_id:
isi:
- '000469415100013'
pmid:
- '31080065'
file:
- access_level: open_access
checksum: aea43726d80e35ce3885073a5f05c3e3
content_type: application/pdf
creator: dernst
date_created: 2020-10-21T07:22:34Z
date_updated: 2020-10-21T07:22:34Z
file_id: '8686'
file_name: 2019_Cell_Shamipour_accepted.pdf
file_size: 3356292
relation: main_file
success: 1
file_date_updated: 2020-10-21T07:22:34Z
has_accepted_license: '1'
intvolume: ' 177'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cell.2019.04.030
month: '05'
oa: 1
oa_version: Published Version
page: 1463-1479.e18
pmid: 1
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '742573'
name: Interaction and feedback between cell mechanics and fate specification in
vertebrate gastrulation
- _id: 268294B6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31639
name: Active mechano-chemical description of the cell cytoskeleton
publication: Cell
publication_identifier:
eissn:
- '10974172'
issn:
- '00928674'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/how-the-cytoplasm-separates-from-the-yolk/
record:
- id: '8350'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Bulk actin dynamics drive phase segregation in zebrafish oocytes
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 177
year: '2019'
...