Mechanical tension and spontaneous muscle twitching precede the formation of cross-striated muscle in vivo

Abstract

Muscle forces are produced by repetitive stereotyped acto-myosin units called sarcomeres. Sarcomeres are chained into linear myofibrils spanning the entire muscle fiber. In mammalian body muscles, myofibrils are aligned laterally resulting in their typical cross-striated morphology. Despite this detailed textbook knowledge about the adult muscle structure, it is still unclear how cross-striated myofibrils are built in vivo. Here, we investigate the morphogenesis of Drosophila abdominal muscles and establish them as in vivo model for cross-striated muscle development. Using live imaging, we find that long immature myofibrils lacking a periodic acto-myosin pattern are built simultaneously in the entire muscle fiber and then align laterally to mature cross-striated myofibrils. Interestingly, laser micro-lesion experiments demonstrate that mechanical tension precedes the formation of the immature myofibrils. Moreover, these immature myofibrils do generate spontaneous Ca2+ dependent contractions in vivo, which when chemically blocked result in cross-striation defects. Together, these results suggest a myofibrillogenesis model, in which mechanical tension and spontaneous muscle twitchings synchronise the simultaneous self-organisation of different sarcomeric protein complexes to build highly regular cross-striated myofibrils spanning throughout large muscle fibers.