Neuronal Activity-Dependent Cell Survival Mediated by Transcription Factor MEF2
10.1126/science.286.5440.785
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

During mammalian development, electrical activity promotes the calcium-dependent survival of neurons that have made appropriate synaptic connections. However, the mechanisms by which calcium mediates neuronal survival during development are not well characterized. A transcription-dependent mechanism was identified by which calcium influx into neurons promoted cell survival. The transcription factor MEF2 was selectively expressed in newly generated postmitotic neurons and was required for the survival of these neurons. Calcium influx into cerebellar granule neurons led to activation of p38 mitogen-activated protein kinase-dependent phosphorylation and activation of MEF2. Once activated, MEF2 regulated neuronal survival by stimulating MEF2-dependent gene transcription. These findings demonstrate that MEF2 is a calcium-regulated transcription factor and define a function for MEF2 during nervous system development that is distinct from previously well-characterized functions of MEF2 during muscle differentiation.

Bibliography

Mao, Z., Bonni, A., Xia, F., Nadal-Vicens, M., & Greenberg, M. E. (1999). Neuronal Activity-Dependent Cell Survival Mediated by Transcription Factor MEF2. Science, 286(5440), 785–790.

Authors 5
  1. Zixu Mao (first)
  2. Azad Bonni (additional)
  3. Fen Xia (additional)
  4. Mireya Nadal-Vicens (additional)
  5. Michael E. Greenberg (additional)
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  34. Supported by a NIH Mental Retardation Research Center grant (P30-HD18655) grants from NIH (NS28829 to M.E.G.) and Daiichi Pharmaceuticals and an NIH training grant (5T32NS07112 to Z.M.). A.B. was supported by a postdoctoral research fellowship for physicians from the Howard Hughes Medical Institute. We thank E. N. Olson and J. D. Molkentin for providing the MEF2CR24L and MEF2CVP16 plasmids J. Han and M. Zhao for the MEF2CS387A and GAL4MEF2C plasmids and M. Wiedmann for technical help. We thank P. Dikkes for assistance in preparing rat brain sections and L. Hu for assistance with antibody preparation. We thank A. Shaywitz and M. Lin for their helpful review of this manuscript.
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:37 a.m.)
Deposited 1 year, 7 months ago (Jan. 13, 2024, 4:51 a.m.)
Indexed 1 month, 1 week ago (July 20, 2025, 12:14 a.m.)
Issued 25 years, 10 months ago (Oct. 22, 1999)
Published 25 years, 10 months ago (Oct. 22, 1999)
Published Print 25 years, 10 months ago (Oct. 22, 1999)
Funders 0

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@article{Mao_1999, title={Neuronal Activity-Dependent Cell Survival Mediated by Transcription Factor MEF2}, volume={286}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.286.5440.785}, DOI={10.1126/science.286.5440.785}, number={5440}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Mao, Zixu and Bonni, Azad and Xia, Fen and Nadal-Vicens, Mireya and Greenberg, Michael E.}, year={1999}, month=oct, pages={785–790} }