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Neuronal Activity-Dependent Cell Survival Mediated by Transcription Factor MEF2
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.
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Cited by
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Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874
Mitogen-activated protein kinases in apoptosis regulation
Wada, T., & Penninger, J. M. (2004) · Oncogene · doi:10.1038/sj.onc.1207556 · Cited by 1,432
G-protein-coupled receptors and signaling networks: emerging paradigms
Marinissen, M. J., & Gutkind, J. S. (2001) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01678-3 · Cited by 1,049
Dolmetsch, R. E., Pajvani, U., Fife, K., Spotts, J. M., & Greenberg, M. E. (2001) · Science · doi:10.1126/science.1063395 · Cited by 900
Self-citationMEF2: a central regulator of diverse developmental programs
Potthoff, M. J., & Olson, E. N. (2007) · Development · doi:10.1242/dev.008367 · Cited by 834
Metadata
- Authors
- Mao, Z., Bonni, A., Xia, F., Nadal-Vicens, M., & Greenberg, M. E.
- Venue
- Science
- Published
- 1999-10-22
- Volume
- 286
- Issue
- 5440
- Pages
- 785-790
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2014764883
- Cited by
- 506
- References
- 0
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- closed
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- Mao, Z., Bonni, A., Xia, F., Nadal-Vicens, M., & Greenberg, M. E. (1999). Neuronal Activity-Dependent Cell Survival Mediated by Transcription Factor MEF2. Science. https://doi.org/10.1126/science.286.5440.785
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