Motor neurons and oligodendrocytes arise from distinct cell lineages by progenitor recruitment

Genes Dev. 2015 Dec 1;29(23):2504-15. doi: 10.1101/gad.271312.115. Epub 2015 Nov 19.

Abstract

During spinal cord development, ventral neural progenitor cells that express the transcription factors Olig1 and Olig2, called pMN progenitors, produce motor neurons and then oligodendrocytes. Whether motor neurons and oligodendrocytes arise from common or distinct progenitors in vivo is not known. Using zebrafish, we found that motor neurons and oligodendrocytes are produced sequentially by distinct progenitors that have distinct origins. When olig2(+) cells were tracked during the peak period of motor neuron formation, most differentiated as motor neurons without further cell division. Using time-lapse imaging, we found that, as motor neurons differentiated, more dorsally positioned neuroepithelial progenitors descended to the pMN domain and initiated olig2 expression. Inhibition of Hedgehog signaling during motor neuron differentiation blocked the ventral movement of progenitors, the progressive initiation of olig2 expression, and oligodendrocyte formation. We therefore propose that the motor neuron-to-oligodendrocyte switch results from Hedgehog-mediated recruitment of glial-fated progenitors to the pMN domain subsequent to neurogenesis.

Keywords: Sonic hedgehog; motor neurons; neural progenitors; oligodendrocytes; pMN domain; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation*
  • Cell Lineage
  • Cell Movement
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / metabolism
  • Motor Neurons / cytology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuroepithelial Cells / cytology
  • Neurogenesis / physiology
  • Oligodendrocyte Transcription Factor 2
  • Oligodendroglia / cytology*
  • Protein Structure, Tertiary
  • Signal Transduction
  • Stem Cells / cytology*
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Hedgehog Proteins
  • Nerve Tissue Proteins
  • Oligodendrocyte Transcription Factor 2
  • Zebrafish Proteins
  • olig2 protein, zebrafish