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

doi:10.1016/j.devcel.2017.04.002

Abstract

SummaryTranscriptional 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.

Highlights

Cell fate decisions in developing tissues are made by gene regulatory networks comprising transcription factors and intercellular signals
We use single-cell transcriptomics to identify the molecular signature of neuromesodermal progenitors (NMPs) and reverse engineer the mechanism that regulates their differentiation
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

Summary

Introduction

Cell fate decisions in developing tissues are made by gene regulatory networks comprising transcription factors and intercellular signals. These networks determine the rate of self-renewal and differentiation to ensure the balanced generation of different cell types and the production of well-proportioned tissues (Stern et al, 2006; Davidson, 2010). The rate at which NMPs are generated, self-renew, and differentiate must be carefully regulated in order to balance the production of different trunk tissues and to prevent the premature or delayed depletion of NMPs that will affect the length of the embryo

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