Muscle development involves complex networks of transcriptional regulators that ensure the specification and diversification of different muscle types. The identification of these factors is essential for the establishment of muscle regenerative therapies that would be effective in curing myopathies. During my thesis, I addressed two aspects of muscle development, firstly the transcriptional regulation of mitochondrial metabolism during adult myogenesis, and secondly the regulation of adult muscle precursor differentiation.
Regarding the first aspect, I identified a novel transcriptional regulator of oxidative metabolism during flight muscle development, M1BP. I have shown that M1BP is a transcriptional activator of genes encoding proteins that constitute and are essential for the formation of mitochondrial respiratory chain complexes during flight muscle development.
In a second step, to better understand the transcriptional regulation of muscle differentiation, I sought to understand the regulatory networks mediated by M1BP. Knowing that M1BP was identified as a Hox gene cofactor, I looked for a Hox gene that would regulate mitochondrial metabolism with M1BP. Correcting a long-standing belief that flight muscle development occurs without the input of Hox transcription factors, I show that the Hox gene Antennapedia (Antp) is expressed in flight muscle precursors and is required for their development. Antp intervenes at several stages of flight muscle development, from the establishment of the progenitor pool in the embryo to myoblast differentiation in the early pupa and is also required to allow for the unique, fibrillar, flight muscle fate acquisition.