EXPRESSION OF MEF2 GENES IN THE MOUSE CENTRAL-NERVOUS-SYSTEM SUGGESTSA ROLE IN NEURONAL MATURATION

Members of the myocyte enhancer factor 2 (MEF2) gene family are expres sed in a dynamic pattern during development of the CNS of pre- and pos tnatal mice. The four MEF2 genes, Mef2A, -B, -C, -D, encode transcript ion factors belonging to the MADS (MCM1-agamous-deficiens-serum respon se factor) superfamily of DNA binding proteins. MEF2 factors have prev iously been shown to be positive regulators of gene expression in term inally differentiated muscle cells. To begin to determine the role of MEF2 factors in CNS development, we used in situ hybridization with ge ne-specific cRNA probes to define the expression patterns of each of t he four Mef2 mRNAs in the developing and mature mouse CNS. Mef2C mRNA was first detected in a ventral portion of the telencephalon at 11.5 d postcoitum (p.c.). By 13.5 d p.c., each of the four Mef2 genes were e xpressed in overlapping yet distinct patterns in regions of the fronta l cortex, midbrain, thalamus, hippocampus, and hindbrain. Temporal and spatial patterns of embryonic Mef2 gene expression appeared to follow gradients of neuron maturation and suggested that the onset of Mef2 g ene expression coincides with withdrawal from the cell cycle and initi ation of neuronal differentiation. This correlation is particularly st riking for Purkinje cells in the cerebellum. Since the molecular mecha nisms that regulate neuron differentiation are unknown, we propose tha t the MEF2 factors are likely to play an important role in this proces s.