Neural Progenitors Adopt Specific Identities by Directly Repressing All Alternative Progenitor Transcriptional Programs

Dev Cell. 2016 Mar 21;36(6):639-53. doi: 10.1016/j.devcel.2016.02.013. Epub 2016 Mar 10.

Abstract

In the vertebrate neural tube, a morphogen-induced transcriptional network produces multiple molecularly distinct progenitor domains, each generating different neuronal subtypes. Using an in vitro differentiation system, we defined gene expression signatures of distinct progenitor populations and identified direct gene-regulatory inputs corresponding to locations of specific transcription factor binding. Combined with targeted perturbations of the network, this revealed a mechanism in which a progenitor identity is installed by active repression of the entire transcriptional programs of other neural progenitor fates. In the ventral neural tube, sonic hedgehog (Shh) signaling, together with broadly expressed transcriptional activators, concurrently activates the gene expression programs of several domains. The specific outcome is selected by repressive input provided by Shh-induced transcription factors that act as the key nodes in the network, enabling progenitors to adopt a single definitive identity from several initially permitted options. Together, the data suggest design principles relevant to many developing tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Body Patterning / genetics
  • Body Patterning / physiology
  • Cell Differentiation / genetics
  • Cell Line
  • Cell Lineage / genetics
  • Chick Embryo
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / metabolism*
  • Oligodendrocyte Transcription Factor 2
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Zebrafish Proteins

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Nkx2.2 protein
  • Nkx6-1 protein, mouse
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Transcription Factors
  • Zebrafish Proteins