Final Report Summary - FLIGHT MUSCLE (Mechanistic dissection of myofibrillogenesis and sarcomerogenesis in insect muscle)
Animals use their muscles for all their daily movements. Hence, muscles must be equipped with a functional contractile apparatus fitting to each muscle type, including powerful but short lasting muscles or less powerful but very enduring muscles. In order to understand the muscle contractile apparatus is built and adjusted to the needs of particular muscle types we have used the fast oscillating Drosophila flight muscles, which enable flight, and compared them to the slow moving Drosophila leg muscles, which enable walking. Using a combination of systematic genetics and high-throughput genomics we have identified the transcription factor Spalt as a master regulator of flight muscle fate and found that Spalt instructs both the transcriptional and alternative splicing program to make fibrillar flight muscles. Spalt together with the RNA-binding protein Arrest control the expression of a bout 700 gene isoforms that together build the fast oscillating insect flight muscles.
In the course of this grant we have established live imaging of the formation and maturation of the contractile apparatus, a process called myofibrillogenesis. Using a laser knife, we found that before the contractile apparatus can assemble mechanical tension is being generated in the muscle. In turn, this tension is important for the correct assembly and maturation of the contractile apparatus, we led to the tension-driven self-organization model of myofibrillogenesis. Thus, myofibrillogenesis is coordinated with the attachment status of the muscle, ensuring proper attachment before high forces are built up. Finally, we have managed to quantify molecular forces across proteins at the muscle attachment site and found that too high individual forces across the attachment protein Talin are avoided by recruiting large amounts of Talin, which can share the mechanical loads.
In the course of this grant we have established live imaging of the formation and maturation of the contractile apparatus, a process called myofibrillogenesis. Using a laser knife, we found that before the contractile apparatus can assemble mechanical tension is being generated in the muscle. In turn, this tension is important for the correct assembly and maturation of the contractile apparatus, we led to the tension-driven self-organization model of myofibrillogenesis. Thus, myofibrillogenesis is coordinated with the attachment status of the muscle, ensuring proper attachment before high forces are built up. Finally, we have managed to quantify molecular forces across proteins at the muscle attachment site and found that too high individual forces across the attachment protein Talin are avoided by recruiting large amounts of Talin, which can share the mechanical loads.