---
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. <i>Developmental
    Cell</i>. 2025;60(4):567-580. doi:<a href="https://doi.org/10.1016/j.devcel.2024.10.024">10.1016/j.devcel.2024.10.024</a>
  apa: Rus, S., Brückner, D., Minchington, T., Greunz, M., Merrin, J., Hannezo, E.
    B., &#38; Kicheva, A. (2025). Self-organized pattern formation in the developing
    mouse neural tube by a temporal relay of BMP signaling. <i>Developmental Cell</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.devcel.2024.10.024">https://doi.org/10.1016/j.devcel.2024.10.024</a>
  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.” <i>Developmental
    Cell</i>. Elsevier, 2025. <a href="https://doi.org/10.1016/j.devcel.2024.10.024">https://doi.org/10.1016/j.devcel.2024.10.024</a>.
  ieee: S. Rus <i>et al.</i>, “Self-organized pattern formation in the developing
    mouse neural tube by a temporal relay of BMP signaling,” <i>Developmental Cell</i>,
    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.” <i>Developmental Cell</i>,
    vol. 60, no. 4, Elsevier, 2025, pp. 567–80, doi:<a href="https://doi.org/10.1016/j.devcel.2024.10.024">10.1016/j.devcel.2024.10.024</a>.
  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: 2026-07-10T22:30:31Z
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:
- access_level: open_access
  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:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 567-580
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
- _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:
  record:
  - id: '19763'
    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. <i>PLoS Computational Biology</i>. 2024;20. doi:<a
    href="https://doi.org/10.1371/journal.pcbi.1012508">10.1371/journal.pcbi.1012508</a>
  apa: Ho, R. D. J. G., Kishi, K., Majka, M., Kicheva, A., &#38; Zagórski, M. P. (2024).
    Dynamics of morphogen source formation in a growing tissue. <i>PLoS Computational
    Biology</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pcbi.1012508">https://doi.org/10.1371/journal.pcbi.1012508</a>
  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.” <i>PLoS
    Computational Biology</i>. Public Library of Science, 2024. <a href="https://doi.org/10.1371/journal.pcbi.1012508">https://doi.org/10.1371/journal.pcbi.1012508</a>.
  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,” <i>PLoS Computational Biology</i>,
    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.” <i>PLoS Computational Biology</i>, vol. 20, e1012508, Public Library
    of Science, 2024, doi:<a href="https://doi.org/10.1371/journal.pcbi.1012508">10.1371/journal.pcbi.1012508</a>.
  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:
- access_level: open_access
  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'
  file_name: 2024_PloSComBio_Ho.pdf
  file_size: 3732443
  relation: main_file
  success: 1
file_date_updated: 2024-10-29T11:59:09Z
has_accepted_license: '1'
intvolume: '        20'
isi: 1
language:
- iso: eng
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. <i>Nature Communications</i>. 2024;15. doi:<a
    href="https://doi.org/10.1038/s41467-024-45148-8">10.1038/s41467-024-45148-8</a>
  apa: Zagorski, M., Brandenberg, N., Lutolf, M., Tkačik, G., Bollenbach, M. T., Briscoe,
    J., &#38; Kicheva, A. (2024). Assessing the precision of morphogen gradients in
    neural tube development. <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-024-45148-8">https://doi.org/10.1038/s41467-024-45148-8</a>
  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.” <i>Nature Communications</i>.
    Springer Nature, 2024. <a href="https://doi.org/10.1038/s41467-024-45148-8">https://doi.org/10.1038/s41467-024-45148-8</a>.
  ieee: M. Zagorski <i>et al.</i>, “Assessing the precision of morphogen gradients
    in neural tube development,” <i>Nature Communications</i>, 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.” <i>Nature Communications</i>, vol. 15, 929, Springer
    Nature, 2024, doi:<a href="https://doi.org/10.1038/s41467-024-45148-8">10.1038/s41467-024-45148-8</a>.
  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:
- access_level: open_access
  checksum: acf75f2b6fa84a64d1f590dd4a53cbf7
  content_type: application/pdf
  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
  relation: main_file
  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'
...
---
_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. <i>Annual
    Review of Cell and Developmental Biology</i>. 2023;39:91-121. doi:<a href="https://doi.org/10.1146/annurev-cellbio-020823-011522">10.1146/annurev-cellbio-020823-011522</a>
  apa: Kicheva, A., &#38; Briscoe, J. (2023). Control of tissue development by morphogens.
    <i>Annual Review of Cell and Developmental Biology</i>. Annual Reviews. <a href="https://doi.org/10.1146/annurev-cellbio-020823-011522">https://doi.org/10.1146/annurev-cellbio-020823-011522</a>
  chicago: Kicheva, Anna, and James Briscoe. “Control of Tissue Development by Morphogens.”
    <i>Annual Review of Cell and Developmental Biology</i>. Annual Reviews, 2023.
    <a href="https://doi.org/10.1146/annurev-cellbio-020823-011522">https://doi.org/10.1146/annurev-cellbio-020823-011522</a>.
  ieee: A. Kicheva and J. Briscoe, “Control of tissue development by morphogens,”
    <i>Annual Review of Cell and Developmental Biology</i>, 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.”
    <i>Annual Review of Cell and Developmental Biology</i>, vol. 39, Annual Reviews,
    2023, pp. 91–121, doi:<a href="https://doi.org/10.1146/annurev-cellbio-020823-011522">10.1146/annurev-cellbio-020823-011522</a>.
  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:
- access_level: open_access
  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
  relation: main_file
  success: 1
file_date_updated: 2023-11-06T09:47:50Z
has_accepted_license: '1'
intvolume: '        39'
isi: 1
language:
- iso: eng
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. <i>Nature Physics</i>.
    2023;19:1050-1058. doi:<a href="https://doi.org/10.1038/s41567-023-01977-w">10.1038/s41567-023-01977-w</a>
  apa: Bocanegra, L., Singh, A., Hannezo, E. B., Zagórski, M. P., &#38; Kicheva, A.
    (2023). Cell cycle dynamics control fluidity of the developing mouse neuroepithelium.
    <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-023-01977-w">https://doi.org/10.1038/s41567-023-01977-w</a>
  chicago: Bocanegra, Laura, Amrita Singh, Edouard B Hannezo, Marcin P Zagórski, and
    Anna Kicheva. “Cell Cycle Dynamics Control Fluidity of the Developing Mouse Neuroepithelium.”
    <i>Nature Physics</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41567-023-01977-w">https://doi.org/10.1038/s41567-023-01977-w</a>.
  ieee: L. Bocanegra, A. Singh, E. B. Hannezo, M. P. Zagórski, and A. Kicheva, “Cell
    cycle dynamics control fluidity of the developing mouse neuroepithelium,” <i>Nature
    Physics</i>, 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.” <i>Nature Physics</i>, vol. 19, Springer Nature, 2023,
    pp. 1050–58, doi:<a href="https://doi.org/10.1038/s41567-023-01977-w">10.1038/s41567-023-01977-w</a>.
  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: 2026-07-10T22:30:17Z
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
  success: 1
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:
  record:
  - id: '13081'
    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. <i>Current Opinion in Systems Biology</i>. 2023;35. doi:<a
    href="https://doi.org/10.1016/j.coisb.2023.100459">10.1016/j.coisb.2023.100459</a>
  apa: Minchington, T., Rus, S., &#38; Kicheva, A. (2023). Control of tissue dimensions
    in the developing neural tube and somites. <i>Current Opinion in Systems Biology</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.coisb.2023.100459">https://doi.org/10.1016/j.coisb.2023.100459</a>
  chicago: Minchington, Thomas, Stefanie Rus, and Anna Kicheva. “Control of Tissue
    Dimensions in the Developing Neural Tube and Somites.” <i>Current Opinion in Systems
    Biology</i>. Elsevier, 2023. <a href="https://doi.org/10.1016/j.coisb.2023.100459">https://doi.org/10.1016/j.coisb.2023.100459</a>.
  ieee: T. Minchington, S. Rus, and A. Kicheva, “Control of tissue dimensions in the
    developing neural tube and somites,” <i>Current Opinion in Systems Biology</i>,
    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.” <i>Current Opinion in Systems Biology</i>, vol. 35,
    100459, Elsevier, 2023, doi:<a href="https://doi.org/10.1016/j.coisb.2023.100459">10.1016/j.coisb.2023.100459</a>.
  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
date_updated: 2026-07-10T22:30:31Z
day: '01'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.1016/j.coisb.2023.100459
file:
- access_level: open_access
  checksum: 8a75c4e29fd9b62e3c50663c2265b173
  content_type: application/pdf
  creator: dernst
  date_created: 2024-01-29T11:06:45Z
  date_updated: 2024-01-29T11:06:45Z
  file_id: '14896'
  file_name: 2023_CurrOpSystBioloy_Minchington.pdf
  file_size: 598842
  relation: main_file
  success: 1
file_date_updated: 2024-01-29T11:06:45Z
has_accepted_license: '1'
intvolume: '        35'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
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
- _id: 9B9B39FA-BA93-11EA-9121-9846C619BF3A
  grant_number: SC19-011
  name: The regulatory logic of pattern formation in the vertebrate dorsal neural
    tube
publication: Current Opinion in Systems Biology
publication_identifier:
  eissn:
  - 2452-3100
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '19763'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Control of tissue dimensions in the developing neural tube and somites
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 35
year: '2023'
...
---
OA_place: publisher
OA_type: hybrid
_id: '7883'
abstract:
- lang: eng
  text: All vertebrates have a spinal cord with dimensions and shape specific to their
    species. Yet how species‐specific organ size and shape are achieved is a fundamental
    unresolved question in biology. The formation and sculpting of organs begins during
    embryonic development. As it develops, the spinal cord extends in anterior–posterior
    direction in synchrony with the overall growth of the body. The dorsoventral (DV)
    and apicobasal lengths of the spinal cord neuroepithelium also change, while at
    the same time a characteristic pattern of neural progenitor subtypes along the
    DV axis is established and elaborated. At the basis of these changes in tissue
    size and shape are biophysical determinants, such as the change in cell number,
    cell size and shape, and anisotropic tissue growth. These processes are controlled
    by global tissue‐scale regulators, such as morphogen signaling gradients as well
    as mechanical forces. Current challenges in the field are to uncover how these
    tissue‐scale regulatory mechanisms are translated to the cellular and molecular
    level, and how regulation of distinct cellular processes gives rise to an overall
    defined size. Addressing these questions will help not only to achieve a better
    understanding of how size is controlled, but also of how tissue size is coordinated
    with the specification of pattern.
acknowledgement: 'Austrian Academy of Sciences, Grant/Award Number: DOC fellowship
  for Katarzyna Kuzmicz-Kowalska; Austrian Science Fund, Grant/Award Number: F78 (Stem
  Cell Modulation); H2020 European Research Council, Grant/Award Number: 680037'
article_number: e383
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Katarzyna
  full_name: Kuzmicz-Kowalska, Katarzyna
  id: 4CED352A-F248-11E8-B48F-1D18A9856A87
  last_name: Kuzmicz-Kowalska
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
citation:
  ama: 'Kuzmicz-Kowalska K, Kicheva A. Regulation of size and scale in vertebrate
    spinal cord development. <i>Wiley Interdisciplinary Reviews: Developmental Biology</i>.
    2021. doi:<a href="https://doi.org/10.1002/wdev.383">10.1002/wdev.383</a>'
  apa: 'Kuzmicz-Kowalska, K., &#38; Kicheva, A. (2021). Regulation of size and scale
    in vertebrate spinal cord development. <i>Wiley Interdisciplinary Reviews: Developmental
    Biology</i>. Wiley. <a href="https://doi.org/10.1002/wdev.383">https://doi.org/10.1002/wdev.383</a>'
  chicago: 'Kuzmicz-Kowalska, Katarzyna, and Anna Kicheva. “Regulation of Size and
    Scale in Vertebrate Spinal Cord Development.” <i>Wiley Interdisciplinary Reviews:
    Developmental Biology</i>. Wiley, 2021. <a href="https://doi.org/10.1002/wdev.383">https://doi.org/10.1002/wdev.383</a>.'
  ieee: 'K. Kuzmicz-Kowalska and A. Kicheva, “Regulation of size and scale in vertebrate
    spinal cord development,” <i>Wiley Interdisciplinary Reviews: Developmental Biology</i>.
    Wiley, 2021.'
  ista: 'Kuzmicz-Kowalska K, Kicheva A. 2021. Regulation of size and scale in vertebrate
    spinal cord development. Wiley Interdisciplinary Reviews: Developmental Biology.,
    e383.'
  mla: 'Kuzmicz-Kowalska, Katarzyna, and Anna Kicheva. “Regulation of Size and Scale
    in Vertebrate Spinal Cord Development.” <i>Wiley Interdisciplinary Reviews: Developmental
    Biology</i>, e383, Wiley, 2021, doi:<a href="https://doi.org/10.1002/wdev.383">10.1002/wdev.383</a>.'
  short: 'K. Kuzmicz-Kowalska, A. Kicheva, Wiley Interdisciplinary Reviews: Developmental
    Biology (2021).'
corr_author: '1'
date_created: 2020-05-24T22:01:00Z
date_published: 2021-04-15T00:00:00Z
date_updated: 2026-07-10T22:30:19Z
day: '15'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.1002/wdev.383
ec_funded: 1
external_id:
  isi:
  - '000531419400001'
  pmid:
  - '32391980'
file:
- access_level: open_access
  checksum: f0a7745d48afa09ea7025e876a0145a8
  content_type: application/pdf
  creator: dernst
  date_created: 2020-11-24T13:11:39Z
  date_updated: 2020-11-24T13:11:39Z
  file_id: '8800'
  file_name: 2020_WIREs_DevBio_KuzmiczKowalska.pdf
  file_size: 2527276
  relation: main_file
  success: 1
file_date_updated: 2020-11-24T13:11:39Z
has_accepted_license: '1'
isi: 1
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: B6FC0238-B512-11E9-945C-1524E6697425
  call_identifier: H2020
  grant_number: '680037'
  name: Coordination of Patterning And Growth In the Spinal Cord
- _id: 267AF0E4-B435-11E9-9278-68D0E5697425
  name: The role of morphogens in the regulation of neural tube growth
- _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: 'Wiley Interdisciplinary Reviews: Developmental Biology'
publication_identifier:
  eissn:
  - 1759-7692
  issn:
  - 1759-7684
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
  record:
  - id: '14323'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Regulation of size and scale in vertebrate spinal cord 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
