---
OA_place: publisher
OA_type: hybrid
_id: '18807'
abstract:
- lang: eng
text: Developing tissues interpret dynamic changes in morphogen activity to generate
cell type diversity. To quantitatively study bone morphogenetic protein (BMP)
signaling dynamics in the mouse neural tube, we developed an embryonic stem cell
differentiation system tailored for growing tissues. Differentiating cells form
striking self-organized patterns of dorsal neural tube cell types driven by sequential
phases of BMP signaling that are observed both in vitro and in vivo. Data-driven
biophysical modeling showed that these dynamics result from coupling fast negative
feedback with slow positive regulation of signaling by the specification of an
endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling
in space, we identify a BMP signaling relay that operates in time. This mechanism
allows for a rapid initial concentration-sensitive response that is robustly terminated,
thereby regulating balanced sequential cell type generation. Our study provides
an experimental and theoretical framework to understand how signaling dynamics
are exploited in developing tissues.
acknowledgement: We thank A. Miller and N. Papalopulu for reagents and J. Briscoe
for comments on the manuscript. Work in the A.K. lab is supported by ISTA; the European
Research Council under Horizon Europe, grant 101044579; and the Austrian Science
Fund (FWF), grant https://doi.org/10.55776/F78. S.L. is supported by Gesellschaft
für Forschungsförderung Niederösterreich m.b.H. fellowship SC19-011. D.B.B. was
supported by the NOMIS foundation as a NOMIS Fellow and by an EMBO Postdoctoral
Fellowship (ALTF 343-2022).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Stefanie
full_name: Rus, Stefanie
id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87
last_name: Rus
orcid: 0000-0001-8703-1093
- first_name: David
full_name: Brückner, David
id: e1e86031-6537-11eb-953a-f7ab92be508d
last_name: Brückner
orcid: 0000-0001-7205-2975
- first_name: Thomas
full_name: Minchington, Thomas
id: 7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f
last_name: Minchington
- first_name: Martina
full_name: Greunz, Martina
id: 48A59534-F248-11E8-B48F-1D18A9856A87
last_name: Greunz
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
citation:
ama: Rus S, Brückner D, Minchington T, et al. Self-organized pattern formation in
the developing mouse neural tube by a temporal relay of BMP signaling. Developmental
Cell. 2025;60(4):567-580. doi:10.1016/j.devcel.2024.10.024
apa: Rus, S., Brückner, D., Minchington, T., Greunz, M., Merrin, J., Hannezo, E.
B., & Kicheva, A. (2025). Self-organized pattern formation in the developing
mouse neural tube by a temporal relay of BMP signaling. Developmental Cell.
Elsevier. https://doi.org/10.1016/j.devcel.2024.10.024
chicago: Rus, Stefanie, David Brückner, Thomas Minchington, Martina Greunz, Jack
Merrin, Edouard B Hannezo, and Anna Kicheva. “Self-Organized Pattern Formation
in the Developing Mouse Neural Tube by a Temporal Relay of BMP Signaling.” Developmental
Cell. Elsevier, 2025. https://doi.org/10.1016/j.devcel.2024.10.024.
ieee: S. Rus et al., “Self-organized pattern formation in the developing
mouse neural tube by a temporal relay of BMP signaling,” Developmental Cell,
vol. 60, no. 4. Elsevier, pp. 567–580, 2025.
ista: Rus S, Brückner D, Minchington T, Greunz M, Merrin J, Hannezo EB, Kicheva
A. 2025. Self-organized pattern formation in the developing mouse neural tube
by a temporal relay of BMP signaling. Developmental Cell. 60(4), 567–580.
mla: Rus, Stefanie, et al. “Self-Organized Pattern Formation in the Developing Mouse
Neural Tube by a Temporal Relay of BMP Signaling.” Developmental Cell,
vol. 60, no. 4, Elsevier, 2025, pp. 567–80, doi:10.1016/j.devcel.2024.10.024.
short: S. Rus, D. Brückner, T. Minchington, M. Greunz, J. Merrin, E.B. Hannezo,
A. Kicheva, Developmental Cell 60 (2025) 567–580.
corr_author: '1'
date_created: 2025-01-09T11:25:47Z
date_published: 2025-02-24T00:00:00Z
date_updated: 2026-08-27T22:30:43Z
day: '24'
ddc:
- '570'
department:
- _id: AnKi
- _id: EdHa
- _id: NanoFab
doi: 10.1016/j.devcel.2024.10.024
external_id:
isi:
- '001434279000001'
pmid:
- '39603235'
file:
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checksum: bb58db4a908a1f4aabe4004706154541
content_type: application/pdf
creator: dernst
date_created: 2025-04-16T10:54:07Z
date_updated: 2025-04-16T10:54:07Z
file_id: '19584'
file_name: 2025_DevelopmentalCell_Lehr.pdf
file_size: 6994499
relation: main_file
success: 1
file_date_updated: 2025-04-16T10:54:07Z
has_accepted_license: '1'
intvolume: ' 60'
isi: 1
issue: '4'
language:
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month: '02'
oa: 1
oa_version: Published Version
page: 567-580
pmid: 1
project:
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grant_number: '101044579'
name: Mechanisms of tissue size regulation in spinal cord development
- _id: 059DF620-7A3F-11EA-A408-12923DDC885E
grant_number: F7802
name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen
control of growth and pattern in the spinal cord
- _id: 9B9B39FA-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-011
name: The regulatory logic of pattern formation in the vertebrate dorsal neural
tube
publication: Developmental Cell
publication_identifier:
issn:
- 1534-5807
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Self-organized pattern formation in the developing mouse neural tube by a temporal
relay of BMP signaling
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: 60
year: '2025'
...
---
APC_amount: 3197,23 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18481'
abstract:
- lang: eng
text: A tight regulation of morphogen production is key for morphogen gradient formation
and thereby for reproducible and organised organ development. Although many genetic
interactions involved in the establishment of morphogen production domains are
known, the biophysical mechanisms of morphogen source formation are poorly understood.
Here we addressed this by focusing on the morphogen Sonic hedgehog (Shh) in the
vertebrate neural tube. Shh is produced by the adjacently located notochord and
by the floor plate of the neural tube. Using a data-constrained computational
screen, we identified different possible mechanisms by which floor plate formation
can occur, only one of which is consistent with experimental data. In this mechanism,
the floor plate is established rapidly in response to Shh from the notochord and
the dynamics of regulatory interactions within the neural tube. In this process,
uniform activators and Shh-dependent repressors are key for establishing the floor
plate size. Subsequently, the floor plate becomes insensitive to Shh and increases
in size due to tissue growth, leading to scaling of the floor plate with neural
tube size. In turn, this results in scaling of the Shh amplitude with tissue growth.
Thus, this mechanism ensures a separation of time scales in floor plate formation,
so that the floor plate domain becomes growth-dependent after an initial rapid
establishment phase. Our study raises the possibility that the time scale separation
between specification and growth might be a common strategy for scaling the morphogen
gradient amplitude in growing organs. The model that we developed provides a new
opportunity for quantitative studies of morphogen source formation in growing
tissues.
acknowledgement: "We thank Martina Greunz-Schindler for technical support, and Thomas
Minchington and James Briscoe for comments on the manuscript.\r\nRDJGH, MM and MZ
were supported by a grant from the Priority Research Area DigiWorld\r\nunder the
Strategic Programme Excellence Initiative at Jagiellonian University. The research\r\nwas
supported by the Polish National Agency for Academic Exchange, PN/PPO/2018/1/00011/U/00001
which paid the salary of MM and MZ up to Feb 2023. The research received support
from National Science Center, Poland, 2021/42/E/NZ2/00188 which paid salary of MZ.
Work in the AK labis supported by ISTA to KK and AK, the European\r\nResearch Council
under Horizon Europe: grant 101044579 to AK, and Austrian Science Fund\r\n(FWF):
Grant DOI 10.55776/F78 to AK. The salaries of AK and KK were paid by ISTA. The funders
had no role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript."
article_number: e1012508
article_processing_charge: No
article_type: original
author:
- first_name: Richard D.J.G.
full_name: Ho, Richard D.J.G.
last_name: Ho
- first_name: Kasumi
full_name: Kishi, Kasumi
id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
last_name: Kishi
orcid: 0000-0001-6060-4795
- first_name: Maciej
full_name: Majka, Maciej
last_name: Majka
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
- first_name: Marcin P
full_name: Zagórski, Marcin P
id: 343DA0DC-F248-11E8-B48F-1D18A9856A87
last_name: Zagórski
orcid: 0000-0001-7896-7762
citation:
ama: Ho RDJG, Kishi K, Majka M, Kicheva A, Zagórski MP. Dynamics of morphogen source
formation in a growing tissue. PLoS Computational Biology. 2024;20. doi:10.1371/journal.pcbi.1012508
apa: Ho, R. D. J. G., Kishi, K., Majka, M., Kicheva, A., & Zagórski, M. P. (2024).
Dynamics of morphogen source formation in a growing tissue. PLoS Computational
Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1012508
chicago: Ho, Richard D.J.G., Kasumi Kishi, Maciej Majka, Anna Kicheva, and Marcin
P Zagórski. “Dynamics of Morphogen Source Formation in a Growing Tissue.” PLoS
Computational Biology. Public Library of Science, 2024. https://doi.org/10.1371/journal.pcbi.1012508.
ieee: R. D. J. G. Ho, K. Kishi, M. Majka, A. Kicheva, and M. P. Zagórski, “Dynamics
of morphogen source formation in a growing tissue,” PLoS Computational Biology,
vol. 20. Public Library of Science, 2024.
ista: Ho RDJG, Kishi K, Majka M, Kicheva A, Zagórski MP. 2024. Dynamics of morphogen
source formation in a growing tissue. PLoS Computational Biology. 20, e1012508.
mla: Ho, Richard D. J. G., et al. “Dynamics of Morphogen Source Formation in a Growing
Tissue.” PLoS Computational Biology, vol. 20, e1012508, Public Library
of Science, 2024, doi:10.1371/journal.pcbi.1012508.
short: R.D.J.G. Ho, K. Kishi, M. Majka, A. Kicheva, M.P. Zagórski, PLoS Computational
Biology 20 (2024).
corr_author: '1'
date_created: 2024-10-27T23:01:45Z
date_published: 2024-10-14T00:00:00Z
date_updated: 2026-04-07T12:31:58Z
day: '14'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.1371/journal.pcbi.1012508
external_id:
isi:
- '001331700300003'
pmid:
- '39401260'
file:
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checksum: 42fa714459943cb3961b40fab8fd82c8
content_type: application/pdf
creator: dernst
date_created: 2024-10-29T11:59:09Z
date_updated: 2024-10-29T11:59:09Z
file_id: '18487'
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file_size: 3732443
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file_date_updated: 2024-10-29T11:59:09Z
has_accepted_license: '1'
intvolume: ' 20'
isi: 1
language:
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month: '10'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa
grant_number: '101044579'
name: Mechanisms of tissue size regulation in spinal cord development
- _id: 059DF620-7A3F-11EA-A408-12923DDC885E
grant_number: F7802
name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen
control of growth and pattern in the spinal cord
publication: PLoS Computational Biology
publication_identifier:
eissn:
- 1553-7358
issn:
- 1553-734X
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '20393'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Dynamics of morphogen source formation in a growing tissue
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 20
year: '2024'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18902'
acknowledgement: 'MZ is supported by National Science Center, Poland, 2021/42/E/NZ2/00188,
the Polish National Agency for Academic Exchange, and by a grant from the Priority
Research Area DigiWorld under the Strategic Programme Excellence Initiative at Jagiellonian
University. Work in JB’s lab is supported by the Francis Crick Institute, which
receives its core funding from Cancer Research UK, the UK Medical Research Council
and Wellcome Trust (all under CC001051). Work in the AK lab is supported by ISTA,
the European Research Council under Horizon Europe: grant 101044579, and Austrian
Science Fund (FWF): F78 (Neural Stem Cell Modulation).'
article_number: '929'
article_processing_charge: Yes
article_type: letter_note
author:
- first_name: Marcin
full_name: Zagorski, Marcin
last_name: Zagorski
- first_name: Nathalie
full_name: Brandenberg, Nathalie
last_name: Brandenberg
- first_name: Matthias
full_name: Lutolf, Matthias
last_name: Lutolf
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
- first_name: James
full_name: Briscoe, James
last_name: Briscoe
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
citation:
ama: Zagorski M, Brandenberg N, Lutolf M, et al. Assessing the precision of morphogen
gradients in neural tube development. Nature Communications. 2024;15. doi:10.1038/s41467-024-45148-8
apa: Zagorski, M., Brandenberg, N., Lutolf, M., Tkačik, G., Bollenbach, M. T., Briscoe,
J., & Kicheva, A. (2024). Assessing the precision of morphogen gradients in
neural tube development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-024-45148-8
chicago: Zagorski, Marcin, Nathalie Brandenberg, Matthias Lutolf, Gašper Tkačik,
Mark Tobias Bollenbach, James Briscoe, and Anna Kicheva. “Assessing the Precision
of Morphogen Gradients in Neural Tube Development.” Nature Communications.
Springer Nature, 2024. https://doi.org/10.1038/s41467-024-45148-8.
ieee: M. Zagorski et al., “Assessing the precision of morphogen gradients
in neural tube development,” Nature Communications, vol. 15. Springer Nature,
2024.
ista: Zagorski M, Brandenberg N, Lutolf M, Tkačik G, Bollenbach MT, Briscoe J, Kicheva
A. 2024. Assessing the precision of morphogen gradients in neural tube development.
Nature Communications. 15, 929.
mla: Zagorski, Marcin, et al. “Assessing the Precision of Morphogen Gradients in
Neural Tube Development.” Nature Communications, vol. 15, 929, Springer
Nature, 2024, doi:10.1038/s41467-024-45148-8.
short: M. Zagorski, N. Brandenberg, M. Lutolf, G. Tkačik, M.T. Bollenbach, J. Briscoe,
A. Kicheva, Nature Communications 15 (2024).
corr_author: '1'
date_created: 2025-01-27T13:01:01Z
date_published: 2024-02-01T00:00:00Z
date_updated: 2025-12-30T10:57:08Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
- _id: AnKi
doi: 10.1038/s41467-024-45148-8
external_id:
isi:
- '001156218500022'
pmid:
- '38302459'
file:
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checksum: acf75f2b6fa84a64d1f590dd4a53cbf7
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creator: dernst
date_created: 2025-01-27T13:04:03Z
date_updated: 2025-01-27T13:04:03Z
file_id: '18903'
file_name: 2024_NatureComm_Zagorski.pdf
file_size: 4723831
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success: 1
file_date_updated: 2025-01-27T13:04:03Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa
grant_number: '101044579'
name: Mechanisms of tissue size regulation in spinal cord development
- _id: 059DF620-7A3F-11EA-A408-12923DDC885E
grant_number: F7802
name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen
control of growth and pattern in the spinal cord
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Assessing the precision of morphogen gradients in neural tube 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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 15
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '17148'
abstract:
- lang: eng
text: During neural tube (NT) development, the notochord induces an organizer, the
floorplate, which secretes Sonic Hedgehog (SHH) to pattern neural progenitors.
Conversely, NT organoids (NTOs) from embryonic stem cells (ESCs) spontaneously
form floorplates without the notochord, demonstrating that stem cells can self-organize
without embryonic inducers. Here, we investigated floorplate self-organization
in clonal mouse NTOs. Expression of the floorplate marker FOXA2 was initially
spatially scattered before resolving into multiple clusters, which underwent competition
and sorting, resulting in a stable “winning” floorplate. We identified that BMP
signaling governed long-range cluster competition. FOXA2+ clusters expressed BMP4,
suppressing FOXA2 in receiving cells while simultaneously expressing the BMP-inhibitor
NOGGIN, promoting cluster persistence. Noggin mutation perturbed floorplate formation
in NTOs and in the NT in vivo at mid/hindbrain regions, demonstrating how the
floorplate can form autonomously without the notochord. Identifying the pathways
governing organizer self-organization is critical for harnessing the developmental
plasticity of stem cells in tissue engineering.
acknowledgement: We thank P. Pasierbek, A.C. Moreno, T. Lendl, and K. Aumayr for microscopy
support; G. Schmauss for FACS support; M. Novatchkova for assistance with Bioinformatic
analyses; J. Ahel, A. Polikarpova, S. Horer, E. Cesare, and E. Norouzi for technical
assistance; A. Meinhardt for supervision; DRESDEN-concept Genome Center, A. Vogt,
A. Sommer, and the Vienna BioCenter NGS facility for RNA sequencing. We are grateful
to M. Placzek and E. Martí for discussions about the floorplate; to S. Shvartsman
for valuable input; to A. Aszodi, W. Masselink, and S. Raiders for advice on statistical
analyses; to J. Cornwall Scoones, G. Martello, and Tanaka lab members for critical
reading of the manuscript; E. Bassat and E. Chatzidaki for contributing schematics;
and to K. Lust for support. This project has received funding from the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
programme (grant agreement ERC AdG 742046) to E.M.T. This research was funded in
whole or in part by the Austrian Science Fund (FWF) (10.55776/F7803-B) (Stem Cell
Modulation) to E.M.T. and A.K., Sir Henry Wellcome postdoctoral fellowship to H.T.S.,
ELBE fellowship to K.I., and National Science Foundation (US) Phy 2013131 to E.S.
The A.K. lab is also supported by ISTA and the European Research Council under Horizon
Europe grant 101044579, and S.L. is supported by Gesellschaft für Forschungsförderung
Niederösterreich m.b.H. fellowship SC19-011. This work was supported in part by
the Francis Crick Institute, which receives its core funding from Cancer Research
UK (CC001051), the UK Medical Research Council (CC001051), and the Wellcome Trust
(CC001051). For the purpose of open access, the authors have applied a CC BY public
copyright license to any author accepted manuscript (AAM) version arising from this
submission.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Teresa
full_name: Krammer, Teresa
last_name: Krammer
- first_name: Hannah T.
full_name: Stuart, Hannah T.
last_name: Stuart
- first_name: Elena
full_name: Gromberg, Elena
last_name: Gromberg
- first_name: Keisuke
full_name: Ishihara, Keisuke
last_name: Ishihara
- first_name: Dillon
full_name: Cislo, Dillon
last_name: Cislo
- first_name: Manuela
full_name: Melchionda, Manuela
last_name: Melchionda
- first_name: Fernando
full_name: Becerril Perez, Fernando
last_name: Becerril Perez
- first_name: Jingkui
full_name: Wang, Jingkui
last_name: Wang
- first_name: Elena
full_name: Costantini, Elena
last_name: Costantini
- first_name: Stefanie
full_name: Rus, Stefanie
id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87
last_name: Rus
orcid: 0000-0001-8703-1093
- first_name: Laura
full_name: Arbanas, Laura
last_name: Arbanas
- first_name: Alexandra
full_name: Hörmann, Alexandra
last_name: Hörmann
- first_name: Ralph A.
full_name: Neumüller, Ralph A.
last_name: Neumüller
- first_name: Nicola
full_name: Elvassore, Nicola
last_name: Elvassore
- first_name: Eric
full_name: Siggia, Eric
last_name: Siggia
- first_name: James
full_name: Briscoe, James
last_name: Briscoe
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
- first_name: Elly M.
full_name: Tanaka, Elly M.
last_name: Tanaka
citation:
ama: Krammer T, Stuart HT, Gromberg E, et al. Mouse neural tube organoids self-organize
floorplate through BMP-mediated cluster competition. Developmental Cell.
2024;59(15):1940-1953.e10. doi:10.1016/j.devcel.2024.04.021
apa: Krammer, T., Stuart, H. T., Gromberg, E., Ishihara, K., Cislo, D., Melchionda,
M., … Tanaka, E. M. (2024). Mouse neural tube organoids self-organize floorplate
through BMP-mediated cluster competition. Developmental Cell. Elsevier.
https://doi.org/10.1016/j.devcel.2024.04.021
chicago: Krammer, Teresa, Hannah T. Stuart, Elena Gromberg, Keisuke Ishihara, Dillon
Cislo, Manuela Melchionda, Fernando Becerril Perez, et al. “Mouse Neural Tube
Organoids Self-Organize Floorplate through BMP-Mediated Cluster Competition.”
Developmental Cell. Elsevier, 2024. https://doi.org/10.1016/j.devcel.2024.04.021.
ieee: T. Krammer et al., “Mouse neural tube organoids self-organize floorplate
through BMP-mediated cluster competition,” Developmental Cell, vol. 59,
no. 15. Elsevier, p. 1940–1953.e10, 2024.
ista: Krammer T, Stuart HT, Gromberg E, Ishihara K, Cislo D, Melchionda M, Becerril
Perez F, Wang J, Costantini E, Rus S, Arbanas L, Hörmann A, Neumüller RA, Elvassore
N, Siggia E, Briscoe J, Kicheva A, Tanaka EM. 2024. Mouse neural tube organoids
self-organize floorplate through BMP-mediated cluster competition. Developmental
Cell. 59(15), 1940–1953.e10.
mla: Krammer, Teresa, et al. “Mouse Neural Tube Organoids Self-Organize Floorplate
through BMP-Mediated Cluster Competition.” Developmental Cell, vol. 59,
no. 15, Elsevier, 2024, p. 1940–1953.e10, doi:10.1016/j.devcel.2024.04.021.
short: T. Krammer, H.T. Stuart, E. Gromberg, K. Ishihara, D. Cislo, M. Melchionda,
F. Becerril Perez, J. Wang, E. Costantini, S. Rus, L. Arbanas, A. Hörmann, R.A.
Neumüller, N. Elvassore, E. Siggia, J. Briscoe, A. Kicheva, E.M. Tanaka, Developmental
Cell 59 (2024) 1940–1953.e10.
date_created: 2024-06-16T22:01:07Z
date_published: 2024-08-01T00:00:00Z
date_updated: 2026-08-27T22:30:43Z
day: '01'
ddc:
- '570'
department:
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doi: 10.1016/j.devcel.2024.04.021
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- _id: 9B9B39FA-BA93-11EA-9121-9846C619BF3A
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name: The regulatory logic of pattern formation in the vertebrate dorsal neural
tube
publication: Developmental Cell
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eissn:
- 1878-1551
issn:
- 1534-5807
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
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scopus_import: '1'
status: public
title: Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster
competition
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OA_place: publisher
OA_type: gold
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abstract:
- lang: eng
text: "Geometrically controlled stem cell differentiation promotes reproducible
pattern formation. Here, we present a protocol to fabricate elastomeric stencils
for patterned stem cell differentiation. We describe procedures for using photolithography
to produce molds, followed by molding polydimethylsiloxane (PDMS) to obtain stencils
with through holes. We then provide instructions for culturing cells on stencils
and, finally, removing stencils to allow colony growth and cell migration. This
approach yields reproducible two-dimensional organoids tailored for quantitative
studies of growth and pattern formation.\r\nFor complete details on the use and
execution of this protocol, please refer to Lehr et al.1"
acknowledged_ssus:
- _id: NanoFab
acknowledgement: We thank the nanofabrication facility at ISTA for technical assistance.
Work in the A.K. lab is supported by ISTA, the European Research Council under Horizon
Europe (grant 101044579), and the Austrian Science Fund (FWF) (grant https://doi.org/10.55776/F78).
S.L. is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H.
fellowship SC19-011.
article_number: '103187'
article_processing_charge: Yes
article_type: original
author:
- first_name: Stefanie
full_name: Rus, Stefanie
id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87
last_name: Rus
orcid: 0000-0001-8703-1093
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Monika Aleksandra
full_name: Kulig, Monika Aleksandra
id: 3331f5ae-e896-11ec-af79-eeb79769bcb7
last_name: Kulig
- first_name: Thomas
full_name: Minchington, Thomas
id: 7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f
last_name: Minchington
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
citation:
ama: Rus S, Merrin J, Kulig MA, Minchington T, Kicheva A. Protocol for fabricating
elastomeric stencils for patterned stem cell differentiation. STAR Protocols.
2024;5(4). doi:10.1016/j.xpro.2024.103187
apa: Rus, S., Merrin, J., Kulig, M. A., Minchington, T., & Kicheva, A. (2024).
Protocol for fabricating elastomeric stencils for patterned stem cell differentiation.
STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2024.103187
chicago: Rus, Stefanie, Jack Merrin, Monika Aleksandra Kulig, Thomas Minchington,
and Anna Kicheva. “Protocol for Fabricating Elastomeric Stencils for Patterned
Stem Cell Differentiation.” STAR Protocols. Elsevier, 2024. https://doi.org/10.1016/j.xpro.2024.103187.
ieee: S. Rus, J. Merrin, M. A. Kulig, T. Minchington, and A. Kicheva, “Protocol
for fabricating elastomeric stencils for patterned stem cell differentiation,”
STAR Protocols, vol. 5, no. 4. Elsevier, 2024.
ista: Rus S, Merrin J, Kulig MA, Minchington T, Kicheva A. 2024. Protocol for fabricating
elastomeric stencils for patterned stem cell differentiation. STAR Protocols.
5(4), 103187.
mla: Rus, Stefanie, et al. “Protocol for Fabricating Elastomeric Stencils for Patterned
Stem Cell Differentiation.” STAR Protocols, vol. 5, no. 4, 103187, Elsevier,
2024, doi:10.1016/j.xpro.2024.103187.
short: S. Rus, J. Merrin, M.A. Kulig, T. Minchington, A. Kicheva, STAR Protocols
5 (2024).
corr_author: '1'
date_created: 2024-12-01T23:01:53Z
date_published: 2024-12-20T00:00:00Z
date_updated: 2026-08-27T22:30:43Z
day: '20'
ddc:
- '570'
department:
- _id: AnKi
- _id: NanoFab
doi: 10.1016/j.xpro.2024.103187
external_id:
pmid:
- '39602310'
file:
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creator: dernst
date_created: 2024-12-03T10:53:23Z
date_updated: 2024-12-03T10:53:23Z
file_id: '18610'
file_name: 2024_STARProtoc_Lehr.pdf
file_size: 4989169
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intvolume: ' 5'
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month: '12'
oa: 1
oa_version: Published Version
pmid: 1
project:
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grant_number: '101044579'
name: Mechanisms of tissue size regulation in spinal cord development
- _id: 9B9B39FA-BA93-11EA-9121-9846C619BF3A
grant_number: SC19-011
name: The regulatory logic of pattern formation in the vertebrate dorsal neural
tube
publication: STAR Protocols
publication_identifier:
eissn:
- 2666-1667
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '19763'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Protocol for fabricating elastomeric stencils for patterned stem cell differentiation
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: 5
year: '2024'
...
---
_id: '14484'
abstract:
- lang: eng
text: Intercellular signaling molecules, known as morphogens, act at a long range
in developing tissues to provide spatial information and control properties such
as cell fate and tissue growth. The production, transport, and removal of morphogens
shape their concentration profiles in time and space. Downstream signaling cascades
and gene regulatory networks within cells then convert the spatiotemporal morphogen
profiles into distinct cellular responses. Current challenges are to understand
the diverse molecular and cellular mechanisms underlying morphogen gradient formation,
as well as the logic of downstream regulatory circuits involved in morphogen interpretation.
This knowledge, combining experimental and theoretical results, is essential to
understand emerging properties of morphogen-controlled systems, such as robustness
and scaling.
acknowledgement: We are grateful to Zena Hadjivasiliou for comments on this article.
A.K. is supported by grants from the European Research Council under the European
Union (EU) Horizon 2020 research and innovation program (680037) and Horizon Europe
(101044579), and the Austrian Science Fund (F78) (Stem Cell Modulation). J.B. is
supported by the Francis Crick Institute, which receives its core funding from Cancer
Research UK (CC001051), the UK Medical Research Council (CC001051), and the Wellcome
Trust (CC001051), and by a grant from the European Research Council under the EU
Horizon 2020 research and innovation program (742138).
article_processing_charge: Yes (in subscription journal)
article_type: review
author:
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
- first_name: James
full_name: Briscoe, James
last_name: Briscoe
citation:
ama: Kicheva A, Briscoe J. Control of tissue development by morphogens. Annual
Review of Cell and Developmental Biology. 2023;39:91-121. doi:10.1146/annurev-cellbio-020823-011522
apa: Kicheva, A., & Briscoe, J. (2023). Control of tissue development by morphogens.
Annual Review of Cell and Developmental Biology. Annual Reviews. https://doi.org/10.1146/annurev-cellbio-020823-011522
chicago: Kicheva, Anna, and James Briscoe. “Control of Tissue Development by Morphogens.”
Annual Review of Cell and Developmental Biology. Annual Reviews, 2023.
https://doi.org/10.1146/annurev-cellbio-020823-011522.
ieee: A. Kicheva and J. Briscoe, “Control of tissue development by morphogens,”
Annual Review of Cell and Developmental Biology, vol. 39. Annual Reviews,
pp. 91–121, 2023.
ista: Kicheva A, Briscoe J. 2023. Control of tissue development by morphogens. Annual
Review of Cell and Developmental Biology. 39, 91–121.
mla: Kicheva, Anna, and James Briscoe. “Control of Tissue Development by Morphogens.”
Annual Review of Cell and Developmental Biology, vol. 39, Annual Reviews,
2023, pp. 91–121, doi:10.1146/annurev-cellbio-020823-011522.
short: A. Kicheva, J. Briscoe, Annual Review of Cell and Developmental Biology 39
(2023) 91–121.
corr_author: '1'
date_created: 2023-11-05T23:00:53Z
date_published: 2023-10-16T00:00:00Z
date_updated: 2025-12-30T10:57:08Z
day: '16'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.1146/annurev-cellbio-020823-011522
ec_funded: 1
external_id:
isi:
- '001082823000006'
pmid:
- '37418774'
file:
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checksum: 461726014cf5907010afbd418d3c13ec
content_type: application/pdf
creator: dernst
date_created: 2023-11-06T09:47:50Z
date_updated: 2023-11-06T09:47:50Z
file_id: '14491'
file_name: 2023_AnnualReviews_Kicheva.pdf
file_size: 434819
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intvolume: ' 39'
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language:
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month: '10'
oa: 1
oa_version: Published Version
page: 91-121
pmid: 1
project:
- _id: B6FC0238-B512-11E9-945C-1524E6697425
call_identifier: H2020
grant_number: '680037'
name: Coordination of Patterning And Growth In the Spinal Cord
- _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa
grant_number: '101044579'
name: Mechanisms of tissue size regulation in spinal cord development
- _id: 059DF620-7A3F-11EA-A408-12923DDC885E
grant_number: F7802
name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen
control of growth and pattern in the spinal cord
publication: Annual Review of Cell and Developmental Biology
publication_identifier:
eissn:
- 1530-8995
issn:
- 1081-0706
publication_status: published
publisher: Annual Reviews
quality_controlled: '1'
scopus_import: '1'
status: public
title: Control of tissue development by morphogens
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 39
year: '2023'
...
---
_id: '12837'
abstract:
- lang: eng
text: As developing tissues grow in size and undergo morphogenetic changes, their
material properties may be altered. Such changes result from tension dynamics
at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms
controlling the physical state of growing tissues are unclear. We found that at
early developmental stages, the epithelium in the developing mouse spinal cord
maintains both high junctional tension and high fluidity. This is achieved via
a mechanism in which interkinetic nuclear movements generate cell area dynamics
that drive extensive cell rearrangements. Over time, the cell proliferation rate
declines, effectively solidifying the tissue. Thus, unlike well-studied jamming
transitions, the solidification uncovered here resembles a glass transition that
depends on the dynamical stresses generated by proliferation and differentiation.
Our finding that the fluidity of developing epithelia is linked to interkinetic
nuclear movements and the dynamics of growth is likely to be relevant to multiple
developing tissues.
acknowledgement: 'We thank S. Hippenmeyer for the reagents and C. P. Heisenberg, J.
Briscoe and K. Page for comments on the manuscript. This work was supported by IST
Austria; the European Research Council under Horizon 2020 research and innovation
programme grant no. 680037 and Horizon Europe grant 101044579 (A.K.); Austrian Science
Fund (FWF): F78 (Stem Cell Modulation) (A.K.); ISTFELLOW postdoctoral program (A.S.);
Narodowe Centrum Nauki, Poland SONATA, 2017/26/D/NZ2/00454 (M.Z.); and the Polish
National Agency for Academic Exchange (M.Z.).'
article_processing_charge: No
article_type: original
author:
- first_name: Laura
full_name: Bocanegra, Laura
id: 4896F754-F248-11E8-B48F-1D18A9856A87
last_name: Bocanegra
- first_name: Amrita
full_name: Singh, Amrita
id: 76250f9f-3a21-11eb-9a80-a6180a0d7958
last_name: Singh
- 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: Marcin P
full_name: Zagórski, Marcin P
id: 343DA0DC-F248-11E8-B48F-1D18A9856A87
last_name: Zagórski
orcid: 0000-0001-7896-7762
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
citation:
ama: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. Cell cycle dynamics
control fluidity of the developing mouse neuroepithelium. Nature Physics.
2023;19:1050-1058. doi:10.1038/s41567-023-01977-w
apa: Bocanegra, L., Singh, A., Hannezo, E. B., Zagórski, M. P., & Kicheva, A.
(2023). Cell cycle dynamics control fluidity of the developing mouse neuroepithelium.
Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-023-01977-w
chicago: Bocanegra, Laura, Amrita Singh, Edouard B Hannezo, Marcin P Zagórski, and
Anna Kicheva. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.”
Nature Physics. Springer Nature, 2023. https://doi.org/10.1038/s41567-023-01977-w.
ieee: L. Bocanegra, A. Singh, E. B. Hannezo, M. P. Zagórski, and A. Kicheva, “Cell
cycle dynamics control fluidity of the developing mouse neuroepithelium,” Nature
Physics, vol. 19. Springer Nature, pp. 1050–1058, 2023.
ista: Bocanegra L, Singh A, Hannezo EB, Zagórski MP, Kicheva A. 2023. Cell cycle
dynamics control fluidity of the developing mouse neuroepithelium. Nature Physics.
19, 1050–1058.
mla: Bocanegra, Laura, et al. “Cell Cycle Dynamics Control Fluidity of the Developing
Mouse Neuroepithelium.” Nature Physics, vol. 19, Springer Nature, 2023,
pp. 1050–58, doi:10.1038/s41567-023-01977-w.
short: L. Bocanegra, A. Singh, E.B. Hannezo, M.P. Zagórski, A. Kicheva, Nature Physics
19 (2023) 1050–1058.
corr_author: '1'
date_created: 2023-04-16T22:01:09Z
date_published: 2023-07-01T00:00:00Z
date_updated: 2026-08-27T22:30:18Z
day: '01'
ddc:
- '570'
department:
- _id: EdHa
- _id: AnKi
doi: 10.1038/s41567-023-01977-w
ec_funded: 1
external_id:
isi:
- '000964029300003'
pmid:
- '37456593'
file:
- access_level: open_access
checksum: 858225a4205b74406e5045006cdd853f
content_type: application/pdf
creator: dernst
date_created: 2023-10-04T11:13:28Z
date_updated: 2023-10-04T11:13:28Z
file_id: '14392'
file_name: 2023_NaturePhysics_Boncanegra.pdf
file_size: 5532285
relation: main_file
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file_date_updated: 2023-10-04T11:13:28Z
has_accepted_license: '1'
intvolume: ' 19'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1050-1058
pmid: 1
project:
- _id: B6FC0238-B512-11E9-945C-1524E6697425
call_identifier: H2020
grant_number: '680037'
name: Coordination of Patterning And Growth In the Spinal Cord
- _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa
grant_number: '101044579'
name: Mechanisms of tissue size regulation in spinal cord development
- _id: 059DF620-7A3F-11EA-A408-12923DDC885E
grant_number: F7802
name: Stem Cell Modulation in Neural Development and Regeneration/ P02-Morphogen
control of growth and pattern in the spinal cord
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Cell cycle dynamics control fluidity of the developing mouse neuroepithelium
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: 19
year: '2023'
...
---
_id: '13136'
abstract:
- lang: eng
text: Despite its fundamental importance for development, the question of how organs
achieve their correct size and shape is poorly understood. This complex process
requires coordination between the generation of cell mass and the morphogenetic
mechanisms that sculpt tissues. These processes are regulated by morphogen signalling
pathways and mechanical forces. Yet, in many systems, it is unclear how biochemical
and mechanical signalling are quantitatively interpreted to determine the behaviours
of individual cells and how they contribute to growth and morphogenesis at the
tissue scale. In this review, we discuss the development of the vertebrate neural
tube and somites as an example of the state of knowledge, as well as the challenges
in understanding the mechanisms of tissue size control in vertebrate organogenesis.
We highlight how the recent advances in stem cell differentiation and organoid
approaches can be harnessed to provide new insights into this question.
acknowledgement: 'We thank J. Briscoe for comments on the manuscript. Work in the
AK lab is supported by ISTA, the European Research Council under Horizon Europe:
grant 101044579, and Austrian Science Fund (FWF): F78 (Stem Cell Modulation). SR
is supported by Gesellschaft für Forschungsförderung Niederösterreich m.b.H. fellowship
SC19-011.'
article_number: '100459'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Thomas
full_name: Minchington, Thomas
id: 7d1648cb-19e9-11eb-8e7a-f8c037fb3e3f
last_name: Minchington
- first_name: Stefanie
full_name: Rus, Stefanie
id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87
last_name: Rus
orcid: 0000-0001-8703-1093
- first_name: Anna
full_name: Kicheva, Anna
id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
last_name: Kicheva
orcid: 0000-0003-4509-4998
citation:
ama: Minchington T, Rus S, Kicheva A. Control of tissue dimensions in the developing
neural tube and somites. Current Opinion in Systems Biology. 2023;35. doi:10.1016/j.coisb.2023.100459
apa: Minchington, T., Rus, S., & Kicheva, A. (2023). Control of tissue dimensions
in the developing neural tube and somites. Current Opinion in Systems Biology.
Elsevier. https://doi.org/10.1016/j.coisb.2023.100459
chicago: Minchington, Thomas, Stefanie Rus, and Anna Kicheva. “Control of Tissue
Dimensions in the Developing Neural Tube and Somites.” Current Opinion in Systems
Biology. Elsevier, 2023. https://doi.org/10.1016/j.coisb.2023.100459.
ieee: T. Minchington, S. Rus, and A. Kicheva, “Control of tissue dimensions in the
developing neural tube and somites,” Current Opinion in Systems Biology,
vol. 35. Elsevier, 2023.
ista: Minchington T, Rus S, Kicheva A. 2023. Control of tissue dimensions in the
developing neural tube and somites. Current Opinion in Systems Biology. 35, 100459.
mla: Minchington, Thomas, et al. “Control of Tissue Dimensions in the Developing
Neural Tube and Somites.” Current Opinion in Systems Biology, vol. 35,
100459, Elsevier, 2023, doi:10.1016/j.coisb.2023.100459.
short: T. Minchington, S. Rus, A. Kicheva, Current Opinion in Systems Biology 35
(2023).
corr_author: '1'
date_created: 2023-06-18T22:00:46Z
date_published: 2023-09-01T00:00:00Z
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title: Control of tissue dimensions in the developing neural tube and somites
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