Home LiteratureArticle Details
PMID: 18599437 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 27 ·2008-07-08 ·Pages 9397-402

Li H, Radford JC, Ragusa MJ, Shea KL, McKercher SR, Zaremba JD, Soussou W, Nie Z, Kang YJ, Nakanishi N, Okamoto S, Roberts AJ, Schwarz JJ, Lipton SA

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.

MeSH Terms
Animals Animals, Newborn Behavior Cell Differentiation Cognition Electrophysiology Embryonic Development MEF2 Transcription Factors Mice Mice, Knockout Mitosis Myogenic Regulatory Factors/metabolism Neocortex/embryology,pathology Neurons/cytology,pathology Phenotype Stem Cells/cytology Transcription Factors/metabolism
Chemicals
MEF2 Transcription Factors Mef2c protein, mouse Myogenic Regulatory Factors Transcription Factors
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Li Hao
Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
Radford Jonathan C
Ragusa Michael J
Shea Katherine L
McKercher Scott R
Zaremba Jeffrey D
Soussou Walid
Nie Zhiguo
Kang Yeon-Joo
Nakanishi Nobuki
Okamoto Shu-ichi
Roberts Amanda J
Schwarz John J
Lipton Stuart A
References (27)
27 references, click to expand
  1. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3.
    Neuron. 2002 Jul 18;35(2):243-54 PMID: 12160743
  2. MeCP2, a key contributor to neurological disease, activates and represses transcription.
    Science. 2008 May 30;320(5880):1224-9 PMID: 18511691
  3. Myocyte enhancer factor (MEF) 2C: a tissue-restricted member of the MEF-2 family of transcription factors.
    Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5282-6 PMID: 8506376
  4. Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number.
    Science. 2006 Feb 17;311(5763):1008-12 PMID: 16484497
  5. Reelin modulates NMDA receptor activity in cortical neurons.
    J Neurosci. 2005 Sep 7;25(36):8209-16 PMID: 16148228
  6. Modulation of neuronal migration by NMDA receptors.
    Science. 1993 Apr 2;260(5104):95-7 PMID: 8096653
  7. The story of Rett syndrome: from clinic to neurobiology.
    Neuron. 2007 Nov 8;56(3):422-37 PMID: 17988628
  8. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation.
    Neuron. 2006 Oct 19;52(2):255-69 PMID: 17046689
  9. MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function.
    Proc Natl Acad Sci U S A. 2008 Jul 8;105(27):9391-6 PMID: 18599438
  10. MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex.
    Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1546-50 PMID: 7679508
  11. Behavioral and anatomical abnormalities in Mecp2 mutant mice: a model for Rett syndrome.
    Neuroscience. 2007 May 25;146(3):907-21 PMID: 17383101
  12. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler.
    Nature. 1995 Apr 20;374(6524):719-23 PMID: 7715726
  13. Mef2 gene expression marks the cardiac and skeletal muscle lineages during mouse embryogenesis.
    Development. 1994 May;120(5):1251-63 PMID: 8026334
  14. The expression of MEF2 genes is implicated in CNS neuronal differentiation.
    Brain Res Mol Brain Res. 1996 Dec;42(2):307-16 PMID: 9013788
  15. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice.
    Nat Genet. 2001 Mar;27(3):327-31 PMID: 11242118
  16. Neurons from radial glia: the consequences of asymmetric inheritance.
    Curr Opin Neurobiol. 2003 Feb;13(1):34-41 PMID: 12593980
  17. Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons.
    Neuron. 1999 Jun;23(2):257-71 PMID: 10399933
  18. Molecular mechanisms controlling cortical gliogenesis.
    Curr Opin Neurobiol. 2002 Jun;12(3):244-9 PMID: 12049929
  19. Radial glial cells as neuronal precursors: a new perspective on the correlation of morphology and lineage restriction in the developing cerebral cortex of mice.
    Brain Res Bull. 2002 Apr;57(6):777-88 PMID: 12031274
  20. Mecp2 deficiency is associated with learning and cognitive deficits and altered gene activity in the hippocampal region of mice.
    Brain. 2006 Apr;129(Pt 4):887-98 PMID: 16467389
  21. Control of mouse cardiac morphogenesis and myogenesis by transcription factor MEF2C.
    Science. 1997 May 30;276(5317):1404-7 PMID: 9162005
  22. Transcriptional activity of MEF2 during mouse embryogenesis monitored with a MEF2-dependent transgene.
    Development. 1999 May;126(10):2045-52 PMID: 10207130
  23. A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation.
    Science. 2006 Feb 17;311(5763):1012-7 PMID: 16484498
  24. Expression of mef2 genes in the mouse central nervous system suggests a role in neuronal maturation.
    J Neurosci. 1995 Aug;15(8):5727-38 PMID: 7643214
  25. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety.
    Nat Genet. 1999 Sep;23(1):99-103 PMID: 10471508
  26. Myocyte enhancer factor 2C as a neurogenic and antiapoptotic transcription factor in murine embryonic stem cells.
    J Neurosci. 2008 Jun 25;28(26):6557-68 PMID: 18579729
  27. Antiapoptotic role of the p38 mitogen-activated protein kinase-myocyte enhancer factor 2 transcription factor pathway during neuronal differentiation.
    Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7561-6 PMID: 10852968
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0802876105
Published
2008-07-08
Epub
2008-00-01
Pages
9397-402
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2453715
Subset
IM
Grants
NINDS NIH HHS · R01 NS044326 · United States
NINDS NIH HHS · P30 NS057096 · United States
NHLBI NIH HHS · R01 HL060853 · United States
NICHD NIH HHS · P01 HD029587 · United States
NICHD NIH HHS · P01 HD29587 · United States
External Links
PubMed source DOI: 10.1073/pnas.0802876105 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2