Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.
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.
Li
Hao
H
Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Radford
Jonathan C
JC
Ragusa
Michael J
MJ
Shea
Katherine L
KL
McKercher
Scott R
SR
Zaremba
Jeffrey D
JD
Soussou
Walid
W
Nie
Zhiguo
Z
Kang
Yeon-Joo
YJ
Nakanishi
Nobuki
N
Okamoto
Shu-ichi
S
Roberts
Amanda J
AJ
Schwarz
John J
JJ
Lipton
Stuart A
SA
D000818:Animals; D000831:Animals, Newborn; D001519:Behavior; D002454:Cell Differentiation; D003071:Cognition; D004594:Electrophysiology; D047108:Embryonic Development; D064326:MEF2 Transcription Factors; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D019579:Neocortex / Q000196:embryology / Q000473:pathology; D009474:Neurons / Q000166:cytology* / Q000473:pathology; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000378:metabolism*
D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors