MEF2 GENE-EXPRESSION MARKS THE CARDIAC AND SKELETAL-MUSCLE LINEAGES DURING MOUSE EMBRYOGENESIS

Members of the MEF2 family of transcription factors bind a conserved A /T-rich sequence in the control regions of many skeletal and cardiac m uscle genes. To begin to assess the roles of tbe different Mef2 genes in the control of muscle gene expression in vivo, we analyzed by in si tu hybridization the expression patterns of the Mef2a, Mef2c and Mef2d genes during mouse embryogenesis. We first detected MEF2C expression at day 7.5 postcoitum (p.c.) in cells of the cardiac mesoderm that giv e rise to the primitive heart tube, making MEF2C one of the earliest m arkers for the cardiac muscle lineage yet described. By day 8.5, MEF2A , MEF2C and MEF2D mRNAs are all detected in the myocardium. By day 9.0 , MEF2C is expressed in rostral myotomes, where its expression lags by about a day behind that of myf5 and several hours behind that of myog enin. MEF2A and MEF2D are expressed at a lower level than MEF2C in the myotome at day 9.5 and are detected in more embryonic tissues than ME F2C. Expression of each of the MEF2 transcripts is observed in muscle- forming regions within the limbs at day 11.5 p.c. and within muscle fi bers throughout the embryo at later developmental stages. The expressi on of MEF2C in the somites and fetal muscle is distinct from that of M EF2A, MEF2D and the myogenic bHLH regulatory genes, suggesting that it may represent a distinct myogenic cell type. Neural crest cells also express high levels of MEF2 mRNAs between days 8.5 and 10.5 of gestati on. After day 12.5 p.c., MEF2 transcripts are detected at high levels in specific regions of the brain and ultimately in a wide range of tis sues. The distinct patterns of expression of the different Mef2 genes during mouse embryogenesis suggest that these genes respond to unique developmental cues and support the notion that their products play rol es in the regulation of muscle-specific transcription during establish ment of the cardiac and skeletal muscle lineages.