Mechanistic dissection of myofibrillogenesis and s.. (FLIGHT MUSCLE)
Mechanistic dissection of myofibrillogenesis and sarcomerogenesis in insect muscle
Start date: Feb 1, 2013,
End date: Jan 31, 2018
Higher animals employ a complex muscle network for their daily movements. Proper execution of movements requires individual muscles to form at the correct positions, connect to proper tendons and produce sufficient force. Muscle development is a multi-step process: myoblasts proliferate, migrate to particular locations and fuse to myotubes. Myotubes target appropriate tendons to establish a stable connection and transition to myofibers by assembling their specific contractile apparatus in a process called myofibrillogenesis. Interestingly, Drosophila adult muscles consist of two major types: tubular striated muscles, e.g. present in legs for walking, and fibrillar flight muscles that power rapid wing oscillations required during flight. The aims of my ERC proposal will address: 1) How do transcriptional networks instruct muscle diversity? 2) Which proteins have an essential role in myofibrillogenesis in different muscle types? 3) How are myofibrils and sarcomeres built in space and time in a muscle specific manner? My entry point is a genome-wide muscle-specific RNAi screen that identified the transcription factor Salm as selector gene for fibrillar flight muscle. Salm alone is sufficient to instruct all specific properties of fibrillar muscle. We will apply a combination of next-generation mRNA sequencing and chromatin immunoprecipitation to dissect the mechanism how Salm initiates myofiber type specification. We will manipulate the identified differentially expressed individual components to assess their mechanistic role in the differential assembly of myofibrils. Detailed in vivo time-lapse analysis of wild-type and mutant muscle combined with biochemical purifications of protein complexes will lead us to a better understanding of the dynamics and molecular constraints of sarcomere formation in each muscle type. Together, this will unravel developmental principles instructing muscle morphogenesis that are conserved to vertebrates and thus are of general interest.
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