Abstract

During early vertebrate development, signals from a special region of the embryo, the organizer, can re-direct the fate of non-neural ectoderm cells to form a complete, patterned nervous system. This is called neural induction and has generally been imagined as a single signalling event, causing a switch of fate. Here we undertake a comprehensive analysis, in very fine time-course, of the events following exposure of competent ectoderm of the chick to the organizer (the tip of the primitive streak, Hensen's node). Using transcriptomics and epigenomics we generate a Gene Regulatory Network comprising 175 transcriptional regulators and 5,614 predicted interactions between them, with fine temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization, single-cell RNA-sequencing and reporter assays we show that the gene regulatory hierarchy of responses to a grafted organizer closely resembles the events of normal neural plate development. The study is accompanied by an extensive resource, including information about conservation of the predicted enhancers in other vertebrates.

Data availability

Full scRNAseq software and pipelines deposited in https://github.com/alexthiery/10x_neural_tubeFull software/scripts/pipelines for GRN construction deposited inhttps://github.com/grace-hc-lu/NI_networkFull sequencing datasets in ArrayExpress under E-MTAB-10409, E-MTAB-10420, E-MTAB-10424, E-MTAB-10426, and E-MTAB-10408.Expression patterns submitted to GEISHA (http://geisha.arizona.edu/geisha/)Code for DREiVe: https://github.com/grace-hc-lu/DREiVe

Article and author information

Author details

  1. Katherine E Trevers

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Hui-Chun Lu

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Youwen Yang

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexandre P Thiery

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Anna C Strobl

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Claire Anderson

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Božena Pálinkášová

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Nidia MM de Oliveira

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Irene M de Almeida

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Mohsin AF Khan

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Natalia Moncaut

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Nicholas M Luscombe

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Leslie Dale

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Andrea Streit

    Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7664-7917
  15. Claudio D Stern

    Department of Cell and Developmental Biology, University College London, London, United Kingdom
    For correspondence
    c.stern@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9907-889X

Funding

National Institute of Mental Health (R01 MH60156)

  • Claudio D Stern

Wellcome Trust (FC010110)

  • Nicholas M Luscombe

Medical Research Council (G0400559)

  • Claudio D Stern

Wellcome Trust (063988)

  • Claudio D Stern

Biotechnology and Biological Sciences Research Council (BB/R003432/1)

  • Claudio D Stern

Biotechnology and Biological Sciences Research Council (BB/K007742/1)

  • Claudio D Stern

Biotechnology and Biological Sciences Research Council (BB/K006207/1)

  • Andrea Streit

Francis Crick Institute

  • Nicholas M Luscombe

Cancer Research UK (FC010110)

  • Nicholas M Luscombe

Medical Research Council (FC010110)

  • Nicholas M Luscombe

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Anne Helene Monsoro-Burq, Institute Curie, France

Version history

  1. Preprint posted: April 16, 2021 (view preprint)
  2. Received: August 19, 2021
  3. Accepted: March 2, 2023
  4. Accepted Manuscript published: March 3, 2023 (version 1)
  5. Version of Record published: March 24, 2023 (version 2)

Copyright

© 2023, Trevers et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Katherine E Trevers
  2. Hui-Chun Lu
  3. Youwen Yang
  4. Alexandre P Thiery
  5. Anna C Strobl
  6. Claire Anderson
  7. Božena Pálinkášová
  8. Nidia MM de Oliveira
  9. Irene M de Almeida
  10. Mohsin AF Khan
  11. Natalia Moncaut
  12. Nicholas M Luscombe
  13. Leslie Dale
  14. Andrea Streit
  15. Claudio D Stern
(2023)
A gene regulatory network for neural induction
eLife 12:e73189.
https://doi.org/10.7554/eLife.73189

Share this article

https://doi.org/10.7554/eLife.73189

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