Olig3 regulates early cerebellar development

Elife. 2021 Feb 16:10:e64684. doi: 10.7554/eLife.64684.

Abstract

The mature cerebellum controls motor skill precision and participates in other sophisticated brain functions that include learning, cognition, and speech. Different types of GABAergic and glutamatergic cerebellar neurons originate in temporal order from two progenitor niches, the ventricular zone and rhombic lip, which express the transcription factors Ptf1a and Atoh1, respectively. However, the molecular machinery required to specify the distinct neuronal types emanating from these progenitor zones is still unclear. Here, we uncover the transcription factor Olig3 as a major determinant in generating the earliest neuronal derivatives emanating from both progenitor zones in mice. In the rhombic lip, Olig3 regulates progenitor cell proliferation. In the ventricular zone, Olig3 safeguards Purkinje cell specification by curtailing the expression of Pax2, a transcription factor that suppresses the Purkinje cell differentiation program. Our work thus defines Olig3 as a key factor in early cerebellar development.

Keywords: Olig3; bHLH transcription factors; cerebellar development; cerebellar hypoplasia; developmental biology; mouse; neuron specification; neuronal fate change; neuroscience.

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*
  • Cell Differentiation
  • Cerebellum / cytology
  • Cerebellum / embryology*
  • Cerebellum / metabolism
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Knockout
  • Neurogenesis
  • Purkinje Cells / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Transcription Factors

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.