Polycomb Protein Eed is Required for Neurogenesis and Cortical Injury Activation in the Subventricular Zone

Cereb Cortex. 2018 Apr 1;28(4):1369-1382. doi: 10.1093/cercor/bhx289.

Abstract

The postnatal subventricular zone (SVZ) harbors neural stem cells (NSCs) that exhibit robust neurogenesis. However, the epigenetic mechanisms that maintain NSCs and regulate neurogenesis remain unclear. We report that label-retaining SVZ NSCs express Eed, the core component of Polycomb repressive complex 2. In vivo and in vitro conditional knockout and knockdown show Eed is necessary for maintaining NSC proliferation, neurogenesis and neurosphere formation. We discovered that Eed functions to maintain p21 protein levels in NSCs by repressing Gata6 transcription. Both Gata6 overexpression and p21 knockdown reduced neurogenesis, while Gata6 knockdown or p21 overexpression partially rescued neurogenesis after Eed loss. Furthermore, genetic deletion of Eed impaired injury induced SVZ proliferation and emigration. These data reveal a novel epigenetic regulated pathway and suggest an essential role for Eed in SVZ homeostasis and injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bromodeoxyuridine / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Cerebral Cortex / injuries*
  • Cerebral Cortex / pathology*
  • Chromatin Immunoprecipitation
  • Disease Models, Animal
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Excitatory Amino Acid Transporter 1 / genetics
  • Excitatory Amino Acid Transporter 1 / metabolism
  • Gene Expression Regulation, Developmental / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Lateral Ventricles / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Neural Stem Cells / pathology
  • Neural Stem Cells / physiology*
  • Neurogenesis / genetics*
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism

Substances

  • Eed protein, mouse
  • Excitatory Amino Acid Transporter 1
  • RNA, Small Interfering
  • Slc1a3 protein, mouse
  • Green Fluorescent Proteins
  • Enhancer of Zeste Homolog 2 Protein
  • Ezh2 protein, mouse
  • Polycomb Repressive Complex 2
  • Bromodeoxyuridine