Lovato, T. | bioRxiv Science

bioRxiv2024

The Drosophila myogenic inhibitor Him gene is essential for adult muscle function and muscle stem cell maintenance

Vertebrate muscle fibres have a population of Muscle Stem Cells (MuSCs), or "satellite cells", vital to muscle growth, homeostasis and repair. In Drosophila, adult MuSCs with similar characteristics have only recently been described. This has opened up the Drosophila system for analysing how MuSCs operate in muscle maintenance, repair and ageing. Here we show that the Him gene is expressed in the adult muscle progenitors (AMPs), or myoblasts, that make the adult Drosophila thoracic flight and jump muscles. Notably, we also show that Him is expressed in the flight muscle MuSCs identifying Him as only the second genetic marker of these insect MuSCs. We then explored Him function. Him mutants have disrupted organisation of the thoracic jump muscle, resulting in reduced jumping ability. Him mutants also have a reduced pool of the myoblasts that will develop into the flight muscles. In the flight muscles themselves, Him mutants have an age-dependent decrease in the number of MuSCs, indicating that Him is required for maintenance of the adult muscle stem cell population. Moreover, this decrease in MuSCs coincides with a functional effect: there is an age-dependent decline in flight ability. Overall, Him is a novel marker of the Drosophila adult MuSC, and is required during ageing both to maintain MuSC number and flight ability.

developmental biology↗

bioRxiv2023

The Drosophila cardiogenic transcription factors Myocyte enhancer factor-2 and Tinman contribute to heart lumen enlargement through direct activation of the collagen gene Multiplexin.

During embryogenesis, the Drosophila heart forms a lumen, the posterior region of which is increased in diameter and corresponds to the heart proper. To identify the transcriptional control of this morphogenetic process, we analyzed the formation and enlargement of the heart lumen in mutants for the myogenic transcription factor gene Myocyte enhancer factor-2 (Mef2). We found that Mef2 contributes to both lumen formation and lumen expansion, the latter through a requirement for both Mef2 and the cardiogenic gene tinman (tin) to activate the collagen gene Multiplexin (Mp). To determine if Tin and MEF2 act directly upon the Mp gene, we identified an enhancer whose activity recapitulates the cardiac expression of Mp. This enhancer contains binding sites for both Tin and MEF2 and is activated in tissue culture by MEF2 but not Tin. We did not observe synergistic activation of the enhancer when the factors were in combination, despite documenting a direct physical interaction between Tin and MEF2 in vitro. In vivo, the Tin sites are required for normal enhancer activity, whereas mutation of the MEF2 sites results in expanded expression of an enhancer-lacZ reporter, suggesting that transcriptional repression may also contribute to regulation of Mp. Our studies underline how transcription factors must utilize combinatorial interactions to achieve organ-specific and region-specific patterns of gene expression and cell morphogenesis.

developmental biology↗