---
OA_place: publisher
_id: '19763'
abstract:
- lang: eng
  text: "Pattern formation in developing organs is controlled by morphogens. These
    signalling\r\nmolecules form concentration gradients across tissues, thereby providing
    positional\r\ninformation that instructs the pattern of cell differentiation.
    Morphogen gradients are highly\r\ndynamic in space and time. Many factors such
    as morphogen production, spreading,\r\ndegradation, cellular rearrangements and
    others could contribute to changes in the gradient\r\nshape, yet how the spatiotemporal
    signalling dynamics arise in many systems is still unclear.\r\nWe studied the
    dynamics of morphogen signalling and tissue patterning in the developing\r\nvertebrate
    neural tube. In this system, neural crest, roof plate and distinct dorsal progenitor\r\nsubtypes
    are specified in a spatially and temporally ordered manner in response to dorsal-toventral
    gradients of BMP and WNT signalling activity. How the BMP and WNT gradients are\r\nestablished
    and interpreted to ensure ordered cell specification is poorly understood.\r\nTo
    address this question, we developed a 2D embryonic stem cell differentiation system
    that\r\ncaptures key features of dorsal neural tube development. In this system,
    differentiated\r\ncolonies display remarkable self-organised pattern formation
    in response to uniformly\r\napplied BMP ligand. We established a method of differentiating
    the colonies using\r\nmicrofabricated stencils, which allowed us to control the
    initial size and shape of colonies\r\nwithout confining cell migration and colony
    growth. This led to highly reproducible pattern\r\nformation that facilitates
    quantification.\r\nUsing this approach, we observed striking two-phase temporal
    dynamics of BMP signalling in\r\nour colonies: a BMP gradient rapidly forms from
    the periphery to the centre of colonies,\r\nsubsequently disappears and is re-established
    again in the second phase. By combining our\r\nquantitative data with a data-driven
    theoretical model, we uncovered a temporal relay\r\nmechanism that underlies this
    biphasic BMP signalling dynamics. The first signalling phase is\r\ncontrolled
    by fast tissue-autonomous negative feedback that restricts the duration of the\r\ninitial
    response to BMP. The early BMP activity gradient moreover controls the spatial\r\norganisation
    of the cell type pattern: the absence of a first phase results in disordered cell\r\ntype
    pattern. The second phase is controlled by slow positive regulation of BMP signalling
    by\r\nthe transcription factor LMX1A, a key regulator of roof plate identity.
    WNT promotes the\r\nsecond phase of BMP signalling via positive feedback on LMX1A.\r\nAltogether,
    the mechanism that we uncovered ensures the coupling of sequential\r\ndevelopmental
    events, making pattern formation spatially and temporally organised.\r\nFurthermore,
    this mechanism allows the BMP signalling pathway to be reused in different\r\ncontexts
    – first for the establishment of the neural plate border, and subsequently for
    dorsal\r\nneural progenitor patterning. Our study supports a general developmental
    principle in which\r\nmultiple morphogens interact with transcriptional networks
    resulting in complex\r\nspatiotemporal signalling dynamics that ultimately drive
    organised pattern formation."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
acknowledgement: "My work would also not have been possible without the Imaging and
  Optics, the Life Science\r\nand the Preclinical Facility of ISTA. Your support has
  facilitated my research substantially. I\r\nalso want to thank the Graduate School
  Office for their never-ending support and their sincere\r\neffort to improve the
  PhD programme of the ISTA even further.\r\nThis work was supported by the Gesellschaft
  für Forschungsförderung Niederösterreich\r\nm.b.H. fellowship (SC19-011). Thank
  you for recognizing the importance of this project."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Stefanie
  full_name: Rus, Stefanie
  id: 4D9EC9B6-F248-11E8-B48F-1D18A9856A87
  last_name: Rus
  orcid: 0000-0001-8703-1093
citation:
  ama: Rus S. Dynamics of morphogen signalling and cell fate decisions in the dorsal
    neural tube. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-19763">10.15479/AT-ISTA-19763</a>
  apa: Rus, S. (2025). <i>Dynamics of morphogen signalling and cell fate decisions
    in the dorsal neural tube</i>. Institute of Science and Technology Austria. <a
    href="https://doi.org/10.15479/AT-ISTA-19763">https://doi.org/10.15479/AT-ISTA-19763</a>
  chicago: Rus, Stefanie. “Dynamics of Morphogen Signalling and Cell Fate Decisions
    in the Dorsal Neural Tube.” Institute of Science and Technology Austria, 2025.
    <a href="https://doi.org/10.15479/AT-ISTA-19763">https://doi.org/10.15479/AT-ISTA-19763</a>.
  ieee: S. Rus, “Dynamics of morphogen signalling and cell fate decisions in the dorsal
    neural tube,” Institute of Science and Technology Austria, 2025.
  ista: Rus S. 2025. Dynamics of morphogen signalling and cell fate decisions in the
    dorsal neural tube. Institute of Science and Technology Austria.
  mla: Rus, Stefanie. <i>Dynamics of Morphogen Signalling and Cell Fate Decisions
    in the Dorsal Neural Tube</i>. Institute of Science and Technology Austria, 2025,
    doi:<a href="https://doi.org/10.15479/AT-ISTA-19763">10.15479/AT-ISTA-19763</a>.
  short: S. Rus, Dynamics of Morphogen Signalling and Cell Fate Decisions in the Dorsal
    Neural Tube, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-05-30T09:14:58Z
date_published: 2025-05-29T00:00:00Z
date_updated: 2026-04-14T09:50:53Z
day: '29'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: AnKi
- _id: GradSch
doi: 10.15479/AT-ISTA-19763
file:
- access_level: open_access
  checksum: 8cd7fe3ca990adbcafdece119aa0973d
  content_type: application/pdf
  creator: cchlebak
  date_created: 2025-05-30T09:10:22Z
  date_updated: 2025-11-30T23:30:02Z
  embargo: 2025-11-30
  file_id: '19764'
  file_name: Thesis_Lehr_PDFA.pdf
  file_size: 42879974
  relation: main_file
- access_level: closed
  checksum: 0c87dd5fc803450a47b20736b5f86a2f
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: cchlebak
  date_created: 2025-05-30T09:31:15Z
  date_updated: 2025-11-30T23:30:02Z
  embargo_to: open_access
  file_id: '19765'
  file_name: Thesis_Lehr_emptyPages.docx
  file_size: 18731094
  relation: source_file
file_date_updated: 2025-11-30T23:30:02Z
has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '129'
project:
- _id: 9B9B39FA-BA93-11EA-9121-9846C619BF3A
  grant_number: SC19-011
  name: The regulatory logic of pattern formation in the vertebrate dorsal neural
    tube
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '18601'
    relation: part_of_dissertation
    status: public
  - id: '17148'
    relation: part_of_dissertation
    status: public
  - id: '18807'
    relation: part_of_dissertation
    status: public
  - id: '13136'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Anna
  full_name: Kicheva, Anna
  id: 3959A2A0-F248-11E8-B48F-1D18A9856A87
  last_name: Kicheva
  orcid: 0000-0003-4509-4998
title: Dynamics of morphogen signalling and cell fate decisions in the dorsal neural
  tube
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
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: 2026-07-17T22:30:31Z
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'
...
---
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: 2026-07-17T22:30:31Z
day: '01'
ddc:
- '570'
department:
- _id: AnKi
doi: 10.1016/j.devcel.2024.04.021
external_id:
  isi:
  - '001289684800001'
  pmid:
  - '38776925'
file:
- access_level: open_access
  checksum: fefdea9c02862b4bb74de49b65ce638a
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-13T10:59:12Z
  date_updated: 2025-01-13T10:59:12Z
  file_id: '18841'
  file_name: 2024_DevelopmentalCell_Krammer.pdf
  file_size: 6249076
  relation: main_file
  success: 1
file_date_updated: 2025-01-13T10:59:12Z
has_accepted_license: '1'
intvolume: '        59'
isi: 1
issue: '15'
language:
- iso: eng
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'
related_material:
  record:
  - id: '19763'
    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
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 59
year: '2024'
...
---
APC_amount: 804 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '18601'
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. <i>STAR Protocols</i>.
    2024;5(4). doi:<a href="https://doi.org/10.1016/j.xpro.2024.103187">10.1016/j.xpro.2024.103187</a>
  apa: Rus, S., Merrin, J., Kulig, M. A., Minchington, T., &#38; Kicheva, A. (2024).
    Protocol for fabricating elastomeric stencils for patterned stem cell differentiation.
    <i>STAR Protocols</i>. Elsevier. <a href="https://doi.org/10.1016/j.xpro.2024.103187">https://doi.org/10.1016/j.xpro.2024.103187</a>
  chicago: Rus, Stefanie, Jack Merrin, Monika Aleksandra Kulig, Thomas Minchington,
    and Anna Kicheva. “Protocol for Fabricating Elastomeric Stencils for Patterned
    Stem Cell Differentiation.” <i>STAR Protocols</i>. Elsevier, 2024. <a href="https://doi.org/10.1016/j.xpro.2024.103187">https://doi.org/10.1016/j.xpro.2024.103187</a>.
  ieee: S. Rus, J. Merrin, M. A. Kulig, T. Minchington, and A. Kicheva, “Protocol
    for fabricating elastomeric stencils for patterned stem cell differentiation,”
    <i>STAR Protocols</i>, 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.” <i>STAR Protocols</i>, vol. 5, no. 4, 103187, Elsevier,
    2024, doi:<a href="https://doi.org/10.1016/j.xpro.2024.103187">10.1016/j.xpro.2024.103187</a>.
  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: 2026-07-17T22:30:30Z
day: '20'
ddc:
- '570'
department:
- _id: AnKi
- _id: NanoFab
doi: 10.1016/j.xpro.2024.103187
external_id:
  pmid:
  - '39602310'
file:
- access_level: open_access
  checksum: 0c61a6f9978608a103865905e06f4581
  content_type: application/pdf
  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
  relation: main_file
  success: 1
file_date_updated: 2024-12-03T10:53:23Z
has_accepted_license: '1'
intvolume: '         5'
issue: '4'
language:
- iso: eng
month: '12'
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: 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: '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: 2026-07-17T22:30:31Z
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'
...
