title: Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo.
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.
authors.affiliation: Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Radford
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ragusa
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Shea
authors.forename: Scott R
authors.initials: SR
authors.lastname: McKercher
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zaremba
authors.forename: Walid
authors.initials: W
authors.lastname: Soussou
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Nie
authors.forename: Yeon-Joo
authors.initials: YJ
authors.lastname: Kang
authors.forename: Nobuki
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: John J
authors.initials: JJ
authors.lastname: Schwarz
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
mesh_terms: 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*
chemical_list: D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors