---
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. <i>Developmental Cell</i>.
    2024;59(15):1940-1953.e10. doi:<a href="https://doi.org/10.1016/j.devcel.2024.04.021">10.1016/j.devcel.2024.04.021</a>
  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. <i>Developmental Cell</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.devcel.2024.04.021">https://doi.org/10.1016/j.devcel.2024.04.021</a>
  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.”
    <i>Developmental Cell</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.devcel.2024.04.021">https://doi.org/10.1016/j.devcel.2024.04.021</a>.
  ieee: T. Krammer <i>et al.</i>, “Mouse neural tube organoids self-organize floorplate
    through BMP-mediated cluster competition,” <i>Developmental Cell</i>, 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.” <i>Developmental Cell</i>, vol. 59,
    no. 15, Elsevier, 2024, p. 1940–1953.e10, doi:<a href="https://doi.org/10.1016/j.devcel.2024.04.021">10.1016/j.devcel.2024.04.021</a>.
  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: 2026-07-11T22:30:28Z
day: '01'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.1016/j.devcel.2024.04.021
external_id:
  isi:
  - '001289684800001'
  pmid:
  - '38776925'
file:
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intvolume: '        59'
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issue: '15'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '08'
oa: 1
oa_version: Published Version
page: 1940-1953.e10
pmid: 1
project:
- _id: bd7e737f-d553-11ed-ba76-d69ffb5ee3aa
  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: Developmental Cell
publication_identifier:
  eissn:
  - 1878-1551
  issn:
  - 1534-5807
publication_status: published
publisher: Elsevier
quality_controlled: '1'
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    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Mouse neural tube organoids self-organize floorplate through BMP-mediated cluster
  competition
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
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  short: CC BY-NC-ND (4.0)
type: journal_article
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volume: 59
year: '2024'
...