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

Robert Mitchell-Gee, Robert Hoff, Kumar Vishal, Daniel Hancock, Sam McKitrick, Cristina Newnes-Querejeta, TyAnna Lovato, Richard Cripps, Michael Taylor
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Abstract

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.
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果蝇肌生成抑制因子 Him 基因对成体肌肉功能和肌肉干细胞维持至关重要
脊椎动物的肌肉纤维中有一群肌肉干细胞(MuSCs)或卫星细胞,它们对肌肉的生长、平衡和修复至关重要。在果蝇中,具有类似特征的成体肌肉干细胞最近才被描述出来。这为分析 MuSCs 如何在肌肉维护、修复和老化过程中发挥作用开辟了果蝇系统。在这里,我们发现Him基因在成体肌肉祖细胞(AMPs)或肌母细胞中表达,而成体肌肉祖细胞是果蝇胸部飞行肌和跳跃肌的制造者。值得注意的是,我们还发现,Him 在飞行肌肉成肌细胞中也有表达,这表明 Him 是这些昆虫成肌细胞的第二个遗传标记。我们随后探索了 Him 的功能。Him突变体的胸跳肌组织结构被破坏,导致跳跃能力下降。Him突变体中发育成飞行肌的肌母细胞数量也有所减少。在飞行肌肉中,Him突变体的MuSCs数量随年龄而减少,这表明Him是维持成体肌肉干细胞群所必需的。此外,MuSCs的减少与功能效应相吻合:飞行能力的下降与年龄有关。总之,Him是果蝇成体肌肉干细胞的一个新标记,在衰老过程中需要它来维持肌肉干细胞的数量和飞行能力。
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