MTOR controls genesis and autophagy of GABAergic interneurons during brain development

Minhan Ka, Amanda L. Smith, Woo Yang Kim

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Interneuron progenitors in the ganglionic eminence of the ventral telencephalon generate most cortical interneurons during brain development. However, the regulatory mechanism of interneuron progenitors remains poorly understood. Here, we show that MTOR (mechanistic target of rapamycin [serine/threonine kinase]) regulates proliferation and macroautophagy/autophagy of interneuron progenitors in the developing ventral telencephalon. To investigate the role of MTOR in interneuron progenitors, we conditionally deleted the Mtor gene in mouse interneuron progenitors and their progeny by using Tg(mI56i-cre,EGFP)1Kc/Dlx5/6-Cre-IRES-EGFP and Nkx2–1-Cre drivers. We found that Mtor deletion markedly reduced the number of interneurons in the cerebral cortex. However, relative positioning of cortical interneurons was normal, suggesting that disruption of progenitor self-renewal caused the decreased number of cortical interneurons in the Mtor-deleted brain. Indeed, Mtor-deleted interneuron progenitors showed abnormal proliferation and cell cycle progression. Additionally, we detected a significant activation of autophagy in Mtor-deleted brain. Our findings suggest that MTOR plays a critical role in the regulation of cortical interneuron number and autophagy in the developing brain.

Original languageEnglish (US)
Pages (from-to)1348-1363
Number of pages16
JournalAutophagy
Volume13
Issue number8
DOIs
StatePublished - Aug 3 2017

Keywords

  • FOXO3
  • GABA
  • LC3
  • MTOR
  • autophagy
  • brain development
  • interneuron
  • neural progenitor
  • neurogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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