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A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.

TitleA Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development.
Publication TypeJournal Article
Year of Publication2017
AuthorsGouti M, Delile J, Stamataki D, Wymeersch FJ, Huang Y, Kleinjung J, Wilson V, Briscoe J
JournalDev Cell
Volume41
Issue3
Pagination243-261.e7
Date Published2017 May 08
ISSN1878-1551
Abstract

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.

DOI10.1016/j.devcel.2017.04.002
Alternate JournalDev. Cell
PubMed ID28457792
PubMed Central IDPMC5425255
Grant List / / Wellcome Trust / United Kingdom
Publication institute
CRM