---
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: 2026-05-08T22:34:10Z
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'
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language:
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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'
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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'
...