Ascl1 Balances Neuronal versus Ependymal Fate in the Spinal Cord Central Canal

Cell Rep. 2019 Aug 27;28(9):2264-2274.e3. doi: 10.1016/j.celrep.2019.07.087.

Abstract

Generation of neuronal types at the right time, location, and number is essential for building a functional nervous system. Significant progress has been reached in understanding the mechanisms that govern neuronal diversity. Cerebrospinal fluid-contacting neurons (CSF-cNs), an intriguing spinal cord central canal population, are produced during advanced developmental stages, simultaneous with glial and ependymal cells. It is unknown how CSF-cNs are specified after the neurogenesis-to-gliogenesis switch. Here, we identify delayed Ascl1 expression in mouse spinal progenitors during the gliogenic phase as key in CSF-cN differentiation. With fate mappings and time-controlled deletions, we demonstrate that CSF-cNs derive from Ascl1-expressing cells and that Ascl1 triggers late neurogenesis in the amniote spinal cord. Ascl1 abrogation transforms prospective CSF-cN progenitors into ependymocytes. These results demonstrate that late spinal progenitors have the potential to produce neurons and that Ascl1 initiates CSF-cN differentiation, controlling the precise neuronal and nonneuronal composition of the spinal central canal.

Keywords: Ascl1; CSF-cN; CSF-contacting neurons; central canal; ependymocytes; late neurogenesis; neural progenitor; neuron specification; spinal cord; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Ependyma / cytology
  • Ependyma / metabolism*
  • Mice
  • Neurogenesis*
  • Neurons / cytology
  • Neurons / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Spinal Cord / metabolism
  • Zebrafish

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors