Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 27, Pages 9397-9402Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0802876105
Keywords
neurogenesis; synaptogenesis; autism; Rett syndrome
Categories
Funding
- NHLBI NIH HHS [R01 HL060853] Funding Source: Medline
- NICHD NIH HHS [P01 HD029587, P01 HD29587] Funding Source: Medline
- NINDS NIH HHS [R01 NS044326, P30 NS057096] Funding Source: Medline
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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.
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