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.

A Postpartum Model in Rat: Behavioral and Gene Expression Changes Induced by Ovarian Steroid Deprivation

“…Myocyte enhancer factor 2A is a transcription factor that plays a critical role in cell differentiation during development of skeletal muscle, as well as the central nervous system (CNS) (64). Although there are no reports of a relationship between MEF2A and mood disorders, our results suggest that decreased MEF2A gene expression after gonadal steroid deprivation could also contribute to the behavioral changes observed.…”

Class II histone deacetylases: versatile regulators

“…[59]). The striking similarity of MEF2 regulation in neurons and its role in neuronal resistance to excitotoxicity suggests that class IIa HDACs also play a significant role in neurons [60][61][62].…”

MEF2C is required for the normal allocation of cells between the ventricular and sinoatrial precursors of the primary heart field

“…TUNEL assays were performed to investigate the possibility of increased apoptosis in the mutant. We had considered apoptosis a likely possibility since the MEF2s are anti-apoptotic in neurons (Mao et al, 1999;Okamoto et al, 2000;Li et al, 2001). Although apoptosis was detected in other regions of the embryo at E8.5, none was detectable in the linear hearts of either wildtype (Fig.…”

“…One of the factors whose genetic ablation causes morphological and transcriptional abnormalities during early cardiogenesis is MEF2C. It is a member of the small MEF2 family of MADS-box containing transcription factors that have been implicated in several fundamental processes including myogenesis, fibertype specification, cardiac hypertrophy, atherosclerosis, and as both an activator and inhibitor of apoptosis (Molkentin et al, 1995;Woronicz et al, 1995;Firulli et al, 1996;Kolodziejczyk et al, 1999;Mao et al, 1999;Youn et al, 1999;Okamoto et al, 2000;Passier et al, 2000;Wu et al, 2000;Dunn et al, 2001;Yan et al, 2001). Deletion of the mef2c gene results in a heart with a small, nonlooping LV, loss of the RV, no trabeculation, and decreased expression of several cardiac-specific genes (Lin et al, , 1998Bi et al, 1999;Bruneau et al, 2000;Liu et al, 2001).…”