A shared transcriptional code orchestrates temporal patterning of the central nervous system

PLoS Biol. 2021 Nov 12;19(11):e3001450. doi: 10.1371/journal.pbio.3001450. eCollection 2021 Nov.

Abstract

The molecular mechanisms that produce the full array of neuronal subtypes in the vertebrate nervous system are incompletely understood. Here, we provide evidence of a global temporal patterning program comprising sets of transcription factors that stratifies neurons based on the developmental time at which they are generated. This transcriptional code acts throughout the central nervous system, in parallel to spatial patterning, thereby increasing the diversity of neurons generated along the neuraxis. We further demonstrate that this temporal program operates in stem cell-derived neurons and is under the control of the TGFβ signaling pathway. Targeted perturbation of components of the temporal program, Nfia and Nfib, reveals their functional requirement for the generation of late-born neuronal subtypes. Together, our results provide evidence for the existence of a previously unappreciated global temporal transcriptional program of neuronal subtype identity and suggest that the integration of spatial and temporal patterning mechanisms diversifies and organizes neuronal subtypes in the vertebrate nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / genetics*
  • Brain / cytology
  • Central Nervous System / metabolism*
  • Gene Expression Regulation, Developmental
  • Mice
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis / physiology
  • Neurons / physiology
  • Retina / cytology
  • Signal Transduction
  • Spinal Cord / cytology
  • Time Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transforming Growth Factor beta / metabolism

Substances

  • Transcription Factors
  • Transforming Growth Factor beta