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

被引：201

作者：

Li, Hao ^{[1
]}

Radford, Jonathan C. ^{[1
]}

Ragusa, Michael J. ^{[2
]}

Shea, Katherine L. ^{[2
]}

McKercher, Scott R. ^{[1
]}

Zaremba, Jeffrey D. ^{[1
]}

Soussou, Walid ^{[1
]}

Nie, Zhiguo ^{[1
]}

Kang, Yeon-Joo ^{[1
]}

Nakanishi, Nobuki ^{[1
]}

Okamoto, Shu-ichi ^{[1
]}

Roberts, Amanda J. ^{[3
]}

Schwarz, John J. ^{[2
]}

Lipton, Stuart A. ^{[1
,3
]}

机构：

[1] Burnham Inst Med Res, Ctr Neurosci Aging & Stem Cell Res, La Jolla, CA 92037 USA

[2] Albany Med Ctr, Ctr Cardiovasc Sci, Albany, NY 12208 USA

[3] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 27期

关键词：

neurogenesis; synaptogenesis; autism; Rett syndrome;

D O I：

10.1073/pnas.0802876105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：9397 / 9402

页数：6

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