A gene regulatory network balances neural and mesoderm specification during vertebrate trunk development

Mina Gouti*, Julien Delile, Despina Stamataki, Filip J. Wymeersch, Yali Huang, Jens Kleinjung, Valerie Wilson, James Briscoe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Transcriptional networks, regulated by extracellular signals, control cell fate decisions and determine the size and composition of developing tissues. One example is the network controlling bipotent neuromesodermal progenitors (NMPs) that fuel embryo elongation by generating spinal cord and trunk mesoderm tissue. Here, we use single-cell transcriptomics to identify the molecular signature of NMPs and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this reveals a transcriptional network that integrates opposing retinoic acid (RA) and Wnt signals to determine the rate at which cells enter and exit the NMP state. RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. Together, the data define a regulatory network architecture that balances the generation of different cell types from bipotential progenitors in order to facilitate orderly axis elongation. Neuromesodermal progenitors (NMPs) generate cells of the spinal cord and somites. Gouti et al. demonstrate that in vitro NMPs resemble in vivo counterparts at the single-cell level and define a regulatory network that balances the generation of neural and mesodermal tissue to facilitate orderly extension of the embryonic axis.

Original languageEnglish
Article numberE7
Pages (from-to)243-261
Number of pages19
JournalDevelopmental Cell
Volume41
Issue number3
Early online date27 Apr 2017
DOIs
Publication statusPublished - 8 May 2017

Keywords / Materials (for Non-textual outputs)

  • Dynamical systems modeling
  • Gene regulatory networks
  • Neuromesodermal progenitors
  • NMPs
  • Retinoic acid
  • Single-cell transcriptome analysis
  • Vertebrate development

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