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Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9397-402. doi: 10.1073/pnas.0802876105. Epub 2008 Jul 1.

Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.

Author information

  • 1Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.

Abstract

Emerging evidence suggests that myocyte enhancer factor 2 (MEF2) transcription factors act as effectors of neurogenesis in the brain, with MEF2C the predominant isoform in developing cerebrocortex. Here, we show that conditional knockout of Mef2c in nestin-expressing neural stem/progenitor cells (NSCs) impaired neuronal differentiation in vivo, resulting in aberrant compaction and smaller somal size. NSC proliferation and survival were not affected. Conditional null mice surviving to adulthood manifested more immature electrophysiological network properties and severe behavioral deficits reminiscent of Rett syndrome, an autism-related disorder. Our data support a crucial role for MEF2C in programming early neuronal differentiation and proper distribution within the layers of the neocortex.

PMID:
18599437
[PubMed - indexed for MEDLINE]
PMCID:
PMC2453715
Free PMC Article

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