A SERIES OF MUTATIONS IN THE D-MEF2 TRANSCRIPTION FACTOR REVEAL MULTIPLE FUNCTIONS IN LARVAL AND ADULT MYOGENESIS IN DROSOPHILA

The D-mef2 gene encodes a MADS domain transcription factor expressed i n differentiated muscles and their precursors in the Drosophila embryo . Embryos deficient for D-MEF2 protein due to a deletion of upstream t ranscriptional control sequences fail to form muscle, suggesting that the gene is required for muscle cell differentiation. To directly demo nstrate a role for D-mef2 in embryonic myogenesis, we isolated gene mu tants containing EMS-induced point mutations, characterized the effect s of these mutations on D-MEF2 protein stability and nuclear localizat ion, and analyzed the resulting muscle phenotypes. Our results show th at in the somatic muscle lineage, D-mef2 is required for both the form ation and patterning of body wall muscle. In the absence of somatic my ogenesis, there is extensive apoptosis among the myoblast cell populat ion. In contrast, in the cardiac muscle lineage, morphogenesis of the dorsal vessel occurs normally but the three myosin subunit genes are n ot expressed. Mutant embryos also exhibit an abnormal midgut morpholog y, which correlates with the absence of alpha(PS2) integrin gene expre ssion and muscle-specific enhancer function, suggesting that D-mef2 re gulates the inflated locus which encodes this integrin subunit. D-MEF2 is also expressed in adepithelial cells and rare D-mef2 transheterozy gous mutant adults fail to ny, consistent with defects observed in the indirect flight muscles. These results demonstrate that the D-mef2 ge ne has multiple functions in myogenesis and tissue morphogenesis durin g Drosophila development. (C) 1995 Academic Press, Inc.