The expression of MEF2 genes is implicated in CNS neuronal differentiation.

The myocyte enhancer factor-2 (MEF2) proteins are transcription factors required for muscle differentiation. In the present study we examined MEF2 expression in developing cerebellar granule neurons. In the developing postnatal cerebellum, RNA blot analysis revealed that MEF2A and MEF2D RNA levels increase after birth. The majority of this increase occurs around postnatal day 9 reaching a peak at postnatal day 15-18 which is maintained in adults. This time course of expression coincides with the expression of GABA(A) receptor alpha6 subunit RNA, a marker for the differentiation of the mature cerebellar granule neurons. We further observed, using the polyclonal antibody generated against an MEF2A peptide, that MEF2 protein expression occurs primarily in the internal granule cell layer of the developing cerebellum. Thus, MEF2 expression increases as granule neurons differentiate and mature. Experiments also indicated that MEF2 expression not only occurs in the cerebellum but also in other regions of the CNS. In adult mice, expression of RNA for the MEF2 isoforms A, C and D occurs throughout the CNS. MEF2A and D expression occurs at highest levels in the olfactory bulb, hippocampus and cerebellum. The expression of MEF2C differs with low levels of expression in the cerebellum and hindbrain. Using the MEF2A polyclonal antibody, we observed a similar adult pattern of expression for the MEF2 protein with high level of expression in the olfactory bulb, cortex, hippocampus, thalamus and cerebellum. These observations suggest that MEF2 molecules may be an important factor involved in CNS neuron differentiation similar to their role in muscle differentiation.