The exon junction complex component Magoh controls brain size by regulating neural stem cell division.

Journal Article (Journal Article)

Brain structure and size require precise division of neural stem cells (NSCs), which self-renew and generate intermediate neural progenitors (INPs) and neurons. The factors that regulate NSCs remain poorly understood, and mechanistic explanations of how aberrant NSC division causes the reduced brain size seen in microcephaly are lacking. Here we show that Magoh, a component of the exon junction complex (EJC) that binds RNA, controls mouse cerebral cortical size by regulating NSC division. Magoh haploinsufficiency causes microcephaly because of INP depletion and neuronal apoptosis. Defective mitosis underlies these phenotypes, as depletion of EJC components disrupts mitotic spindle orientation and integrity, chromosome number and genomic stability. In utero rescue experiments showed that a key function of Magoh is to control levels of the microcephaly-associated protein Lis1 during neurogenesis. Our results uncover requirements for the EJC in brain development, NSC maintenance and mitosis, thereby implicating this complex in the pathogenesis of microcephaly.

Full Text

Duke Authors

Cited Authors

  • Silver, DL; Watkins-Chow, DE; Schreck, KC; Pierfelice, TJ; Larson, DM; Burnetti, AJ; Liaw, H-J; Myung, K; Walsh, CA; Gaiano, N; Pavan, WJ

Published Date

  • May 2010

Published In

Volume / Issue

  • 13 / 5

Start / End Page

  • 551 - 558

PubMed ID

  • 20364144

Pubmed Central ID

  • PMC2860667

Electronic International Standard Serial Number (EISSN)

  • 1546-1726

Digital Object Identifier (DOI)

  • 10.1038/nn.2527


  • eng

Conference Location

  • United States