A gene regulatory network for neural induction
- University College London, United Kingdom
- King's College London, United Kingdom
- The Francis Crick Institute, United Kingdom
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
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
- Anne Helene Monsoro-Burq, Institute Curie, France
Version history
- Preprint posted: April 16, 2021 (view preprint)
- Received: August 19, 2021
- Accepted: March 2, 2023
- Accepted Manuscript published: March 3, 2023 (version 1)
- 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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A gene regulatory network for neural induction
eLife 12:e73189.
https://doi.org/10.7554/eLife.73189
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