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

Publication ,  Journal Article
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 in: Nat Neurosci
May 2010

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.

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Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

May 2010

Volume

13

Issue

5

Start / End Page

551 / 558

Location

United States

Related Subject Headings

  • Transfection
  • T-Box Domain Proteins
  • Stem Cells
  • Repressor Proteins
  • RNA, Messenger
  • RNA Interference
  • Paired Box Transcription Factors
  • PAX6 Transcription Factor
  • Organ Size
  • Oligonucleotide Array Sequence Analysis
 

Citation

APA
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ICMJE
MLA
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Silver, D. L., Watkins-Chow, D. E., Schreck, K. C., Pierfelice, T. J., Larson, D. M., Burnetti, A. J., … Pavan, W. J. (2010). The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nat Neurosci, 13(5), 551–558. https://doi.org/10.1038/nn.2527
Silver, Debra L., Dawn E. Watkins-Chow, Karisa C. Schreck, Tarran J. Pierfelice, Denise M. Larson, Anthony J. Burnetti, Hung-Jiun Liaw, et al. “The exon junction complex component Magoh controls brain size by regulating neural stem cell division.Nat Neurosci 13, no. 5 (May 2010): 551–58. https://doi.org/10.1038/nn.2527.
Silver DL, Watkins-Chow DE, Schreck KC, Pierfelice TJ, Larson DM, Burnetti AJ, et al. The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nat Neurosci. 2010 May;13(5):551–8.
Silver, Debra L., et al. “The exon junction complex component Magoh controls brain size by regulating neural stem cell division.Nat Neurosci, vol. 13, no. 5, May 2010, pp. 551–58. Pubmed, doi:10.1038/nn.2527.
Silver DL, Watkins-Chow DE, Schreck KC, Pierfelice TJ, Larson DM, Burnetti AJ, Liaw H-J, Myung K, Walsh CA, Gaiano N, Pavan WJ. The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nat Neurosci. 2010 May;13(5):551–558.

Published In

Nat Neurosci

DOI

EISSN

1546-1726

Publication Date

May 2010

Volume

13

Issue

5

Start / End Page

551 / 558

Location

United States

Related Subject Headings

  • Transfection
  • T-Box Domain Proteins
  • Stem Cells
  • Repressor Proteins
  • RNA, Messenger
  • RNA Interference
  • Paired Box Transcription Factors
  • PAX6 Transcription Factor
  • Organ Size
  • Oligonucleotide Array Sequence Analysis