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The Journal of Neuroscience, June 25, 2008, 28(26):6557-6568; doi:10.1523/JNEUROSCI.0134-08.2008

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Development/Plasticity/Repair
Myocyte Enhancer Factor 2C as a Neurogenic and Antiapoptotic Transcription Factor in Murine Embryonic Stem Cells

Zhen Li,1 * Scott R. McKercher,1 * Jiankun Cui,1 Zhiguo Nie,1 Walid Soussou,1 Amanda J. Roberts,2 Tina Sallmen,1 Jeffrey H. Lipton,1 Maria Talantova,1 Shu-ichi Okamoto,1 and Stuart A. Lipton1,2

1Center for Neuroscience, Aging, and Stem Cell Research, Burnham Institute for Medical Research, and 2Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California 92037

Correspondence should be addressed to Stuart A. Lipton, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037. Email: slipton{at}burnham.org

Cell-based therapies require a reliable source of cells that can be easily grown, undergo directed differentiation, and remain viable after transplantation. Here, we generated stably transformed murine ES (embryonic stem) cells that express a constitutively active form of myocyte enhancer factor 2C (MEF2CA). MEF2C has been implicated as a calcium-dependent transcription factor that enhances survival and affects synapse formation of neurons as well as differentiation of cardiomyocytes. We now report that expression of MEF2CA, both in vitro and in vivo, under regulation of the nestin enhancer effectively produces "neuronal" progenitor cells that differentiate into a virtually pure population of neurons. Histological, electrophysiological, and behavioral analyses demonstrate that MEF2C-directed neuronal progenitor cells transplanted into a mouse model of cerebral ischemia can successfully differentiate into functioning neurons and ameliorate stroke-induced behavioral deficits.

Key words: MEF2C; neuronal progenitor cell; embryonic stem cells; neurogenesis; antiapoptotic; transplantation

Received Jan. 11, 2008; revised April 23, 2008; accepted May 13, 2008.

Correspondence should be addressed to Stuart A. Lipton, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037. Email: slipton{at}burnham.org




This article has been cited by other articles:


Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Li, J. C. Radford, M. J. Ragusa, K. L. Shea, S. R. McKercher, J. D. Zaremba, W. Soussou, Z. Nie, Y.-J. Kang, N. Nakanishi, et al.
Transcription factor MEF2C influences neural stem/progenitor cell differentiation and maturation in vivo
PNAS, July 8, 2008; 105(27): 9397 - 9402.
[Abstract] [Full Text] [PDF]


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