SMAD4 is essential for generating subtypes of neurons during cerebellar development

Marie Fernandes, Michelle Antoine, Jean M. Hébert

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cerebellum development involves the coordinated production of multiple neuronal cell types. The cerebellar primordium contains two germinative zones, the rhombic lip (RL) and the ventricular zone (VZ), which generate different types of glutamatergic and GABAergic neurons, respectively. What regulates the specification and production of glutamatergic and GABAergic neurons as well as the subtypes for each of these two broad classes remains largely unknown. Here we demonstrate with conditional genetic approaches in mice that SMAD4, a major mediator of BMP and TGFβ signaling, is required early in cerebellar development for maintaining the RL and generating subsets of RL-derived glutamatergic neurons, namely neurons of the deep cerebellar nuclei, unipolar brush cells, and the late cohort of granule cell precursors (GCPs). The early cohort of GCPs, despite being deficient for SMAD4, is still generated. In addition, the numbers of GABAergic neurons are reduced in the mutant and the distribution of Purkinje cells becomes abnormal. These studies demonstrate a temporally and spatially restricted requirement for SMAD4 in generating subtypes of cerebellar neurons.

Original languageEnglish (US)
Pages (from-to)82-90
Number of pages9
JournalDevelopmental Biology
Volume365
Issue number1
DOIs
StatePublished - May 1 2012

Keywords

  • Deep cerebellar nuclei
  • Granule cell precursor
  • Mouse
  • Rhombic lip
  • SMAD4
  • Unipolar brush cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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