UC San Diego

The study of muscle development and the transcription factors involved in this process is important for advancing our understanding of muscle biology, physiology, and pathology, with potential implications for human health, performance, and disease treatment. The Myocyte enhancer factor-2 (MEF2) and the invertebrate ortholog to Mohawk (Mkx), CG11617, transcription factors play crucial roles in orchestrating muscle differentiation and fiber type specification. RNA-sequencing (RNA-seq) and immunofluorescence reveal that overexpression of MEF2 activates myogenesis in imaginal wing disc myoblasts by inducing sarcomere-like structures, significantly upregulating muscle gene expression, especially those important for myofibril formation and function, and primarily activating the embryonic and larval myogenic program. This broad activation of the embryonic and larval myogenic program suggests that additional regulatory factors are necessary to promote adult muscle-specific programs.The Drosophila CG11617 may be essential in promoting the adult muscle-specific program based on previous research focused on the mammalian ortholog, Mkx, which promotes slow fiber type specification. Our study found that CG11617 is essential for muscle development and proper myofibril formation, and it has nuclear localization in indirect flight muscles (IFMs) and nuclear and cytoplasmic localization in jump muscles. CG11617 knockdown mutants also display lethality at the pharate adult stage, with disorganized IFM myofibrils and the absence of jump muscles, indicating its critical role in muscle structure integrity. Furthermore, the RNA-sequencing analysis of CG11617 knockdown mutants reveals significant upregulation of upheld, which encodes Troponin T, a gene crucial for muscle structure and function. Overexpression of Troponin T leads to muscle degeneration and dysfunction, potentially explaining the severe phenotypes observed in CG11617 knockdown mutants. Despite these insights, the precise mechanistic role of CG11617 in muscle fiber specification remains unclear. Our findings highlight the multifaceted roles of MEF2 and CG11617 in muscle development and reveal the need for further research to elucidate the regulatory mechanisms governing skeletal muscle differentiation and function.