Drosophila Lame duck, a novel member of the Gli superfamily, acts as a keyregulator of myogenesis by controlling fusion-competent myoblast development

A hallmark of mature skeletal muscles is the presence of multinucleate musc le fibers. In Drosophila, the formation of muscle syncytia requires the coo perative participation of two types of myoblasts, founder cells and fusion- competent myoblasts. We show that a newly identified gene, lame duck (lmd), has an essential regulatory role in the specification and function of fusi on-competent myoblasts. Embryos that lack lmd function show a loss of expre ssion of two key differentiation and fusion genes, Mef2 and sticks-and-ston es, in fusion-competent myoblasts and are completely devoid of multinucleat e muscle fibers. By contrast, founder cells are specified and retain their capability to differentiate into mononucleate muscle cells. lmd encodes a n ovel member of the Gli superfamily of transcription factors and is expresse d in fusion-competent myoblasts and their precursors in a Wingless- and Not ch-dependent manner. The activity of the Lmd protein appears to be addition ally controlled by its differential cytoplasmic versus nuclear localization . Results from an independent molecular screen for binding factors to a myo blast-specific Mef2 enhancer further demonstrate that Lmd is a direct trans criptional regulator of Mef2 in fusion-competent myoblasts.