A transcriptional code for muscle fiber identity in Drosophila. Anton L. Bryantsev¹, Sandy Duong¹, Tonya M. Brunetti¹, Maria B. Chechenova¹, TyAnna L. Lovato¹, Cloyce Nelson¹, Elizabeth Shaw¹, Juli D. Uhl², Brian Gebelein², Richard M. Cripps¹. 1) Department of Biology, University of New Mexico, Albuquerque, NM; 2) Division of Dev. Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

   In this study we define a molecular switch that specifies muscle fiber fate in adult Drosophila flies, via activity of the homeodomain proteins Extradenticle (Exd) and Homothorax (Hth). The genes exd and hth are expressed in the fibrillar indirect flight muscles, but not in tubular jump muscles. When expression of exd or hth is knocked down, the flight muscles are transformed into a jump muscle fate. Conversely, if exd and hth are forcefully expressed in the jump muscles, these fibers now become flight muscles. In the flight muscles, exd and hth are genetically upstream of another muscle identity gene, salm. We further demonstrate that exd and hth are direct transcriptional regulators of the signature flight muscle structural gene, Actin88F, indicating that these factors represent a molecular switch to regulate muscle fiber fate. We also demonstrate that Exd and Hth impact muscle identity in other somatic muscles of the body, by cooperating with Hox factors. Since mammalian orthologs of exd and hth also contribute to muscle gene regulation, our study suggests that an evolutionarily-conserved genetic pathway determines muscle fiber differentiation.