Myocyte-specific enhancer binding factor 2C expression in fetal mouse brain development

Abstract

We have previously found that myocyte-specific enhancer binding factor 2C (MEF2C) is expressed in the brain, where it is found at high levels in the developing cerebral cortex. We have now examined MEF2C expression in fetal mouse brain by in situ hybridization and by immunohistochemistry from E11 to E17, the period when most cortical neurons are born. The distribution of MEF2C mRNA detected by in situ hybridization closely resembles that of MEF2C immunoreactivity. MEF2C is not present in proliferative zones in the brain. It is present at high levels in cells that have migrated to the subplate and cortical plate. MEF2C is also found in the olfactory blub at high levels and at lower levels in hippocampus, basal forebrain, striatum, cerebellum, and inferior colliculus, and in some nuclei of the hypothalamus, thalamus and brainstem. The pattern of expression suggests that MEF2C is expressed in a subset of postmitotic neurons in the brain and that it may therefore function to promote terminal differentiation of the cells that express it.

Inactivation of the Myocyte Enhancer Factor-2 Repressor Histone Deacetylase-5 by Endogenous Ca2//Calmodulin-dependent Kinase II Promotes Depolarization-mediated Cerebellar Granule Neuron Survival

“…The expression of MEF2 proteins in the developing CNS is regulated temporally and spatially in an isoform-specific manner, and coincides with neuronal maturation. For example, cerebral cortical neuron development is associated with changes in the expression of MEF2C (35)(36)(37), whereas CGN maturation is coupled to enhanced expression of MEF2A and MEF2D (9). Their differential tissue distribution suggests that MEF2 proteins may be regulated in an isoform-specific manner.…”

MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders

“…However, the functional role(s) of MEF2C in early neuronal development, particularly in the neocortex, remains unclear. In the central nervous system, MEF2C is highly expressed very early in brain development (~E11.5), and its expression is enriched in differentiated forebrain neurons within the neocortex and dentate gyrus (Lyons et al, 1995; Leifer et al, 1993, 1997). Here, we sought to evaluate the role of MEF2C in differentiated cortical excitatory neurons, and to determine whether loss of MEF2C function in these neuronal populations might produce behavioral and synaptic phenotypes with potential relevance to its associated neurodevelopmental disorders.…”

Myocyte-specific enhancer binding factor 2C (MEF2C) expression in the dentate gyrus during development and after pilocarpine-induced status epilepticus: a preliminary report

“…During development, four MEF2 genes (A, B, C, D) are expressed in spatially and temporally specific patterns during brain development, suggesting that, similar to its expression pattern in striated muscle, MEF2 gene expression in the CNS occurs in neurons exiting the cell cycle and entering differentiation 10 . In addition, human studies using immunocytochemical localization of MEF2C in hippocampal surgical specimens revealed immunoreactivity in nuclei of dentate granule cells and the hilus of dentate gyrus, supporting the concept of a role for MEF2C in postmitotic neuronal differentiation 4 . Given that, the results of this study also showed that MEF2C is expressed in dentate granule cells during specific developmental stages, it seems quite possible that MEF2C is involved is in regulating dentate gyrus development.…”

“…It has been known that MEF2C is expressed in a dynamic pattern during development and in the mature mouse CNS, suggesting that the molecule may play an important role at different stages of neuronal differentiation and/or maturation 4,10 . Here it was demonstrated that MEF2C is up-regulated during development and in the adult rat dentate gyrus following SE, suggesting that MEF2C may also be involved in seizure-induced plasticity.…”

“…The myocyte-specific enhancer binding factor 2C (MEF2C), a member of the MEF2 sub-family of the MADS gene family, is a transcription factor expressed at high levels in the brain and has been implicated in the development of neurons 4 . MEF2C binds with basic helix-loop-helix (bHLH) proteins 5 , which in the brain are responsible for neural determination or differentiation 6 .…”