View Program - 63rd Annual Drosophila Research Conference

The mammalian Mohawk transcription factor is known to be expressed in embryonic precursors of skeletal muscle and functions by regulating the transcription of slow-twitch myosin-heavy-chain isoform expression in fast-twitch muscle fibers, through Sox6 repression, during muscle development. However, we do not fully understand its mechanistic role in invertebrate skeletal muscle development. By using the Drosophila melanogaster Mohawk ortholog, termed CG11617, we first analyzed CG11617 localization. Thoracic flight muscles reveal nuclear CG11617 localization whereas the tergal depressor of the trochanter muscles (TDT, or jump muscles) reveal nuclear and cytoplasmic localization between the myofibrils. Analysis of CG11617 knockdown animals revealed that these flies are lethal in the pharate adult stage. Upon examination, these mutant flies showed fibrillar disorganization of indirect flight muscles, the absence of jump muscles, and a significant decrease in imaginal wing disc myoblasts compared to the wild-type. Together, these findings may account for the overall skeletal muscle impairment and pupal lethality observed in the knockdowns. Furthermore, utilizing Gal4 driver lines containing fiber-specific enhancer-lacZ constructs, to follow muscle fiber fate, we observed a fibrillar muscle to tubular muscle identity switch in these mutant flies. Overall, these findings suggest that CG11617 may skew skeletal muscle precursor differentiation towards one fiber-type versus another, and CG11617 is a determinant of skeletal muscle fiber-type specification and differentiation.

Defining the Role of CG11617 in the Transcriptional Control of Muscle Development in Drosophila melanogaster