|Cross-section of an adult Drosophila. Flight muscles are in blue, other muscles in green.||Drosophila in full flight.|
All higher animals require a sophisticated muscle-tendon network for survival and their daily movements. The fruit fly Drosophila utilises its muscles to digest food, to pump hemolymph, and for different behaviors such as walking, mating or flying.
Similar to vertebrates, Drosophila muscle formation is a multi-step process. Myoblasts proliferate and migrate to sites of myogenesis, where they fuse to myotubes. Myotubes search for their proper targets, the tendon attachment sites located in the epidermis, and establish a stable connection to them that mechanically resists future muscle contractions. Finally, myofibrils and sarcomeres assemble within the myofiber to power the future contractions.
Drosophila offers both powerful imaging methods to investigate the dynamics of muscle morphogenesis and systematic genetics to functionally dissect its different steps. Combined with next generation sequencing and high-throughput genomic tagging approaches, Drosophila is ideal to understand the mechanistic basis of muscle development and function. As most molecular players as well as developmental principles are conserved, new insights are also applicable to vertebrate muscle biology.
The Drosophila embryonic body muscles display a very stereotyped pattern in each segment and are thus an ideal system to investigate how each muscle finds and recognises its defined tendon cell target in the epidermis. We follow muscle migration, muslce-tendon targeting and attachment by time-lapse microscopy in living embryos (see movie). We identified Kon-tiki, a putative receptor located at the muscle tips that mediates muscle - tendon recognition during muscle targeting. Currently, we are dissecting the mechanism how Kon-tiki recognises tendons.
Drosophila adult muscles are built from stem cell-like myoblasts during pupal development. Most muscles form de novo from myoblasts only, or in case of the dorsal-longitudinal flight muscles by a regenerative mode in which myoblasts fuse with larval template muscles.
After targeting and stable attachment of muscles to tendons, myofibrillogenesis and sarcomerogenesis forms the muscle's contractile apparatus. Interestingly, adult muscle are functionally different, which is reflected by the architecture of their contractile filaments. Indirect flight muscles show a particular fibrillar organisation of their myofibrils and start contracting when stretched. This is essential to power the 200 Hz wing osciallations during flight. In contrast, other muscles such as leg muscles have a tubular fiber organisation and are not stretch-activated.
We are interested in the morphogenesis of adult muscles:
How are different muscles formed during development?
How do they identify and connect to tendons?
How do they build myofibrills and sarcomeres?
We performed a systematic, genome-wide, muscle-specific RNAi screen in which we tested the function of most genes in muscle morphogenesis. We recently identified the transcription factor Spalt major (Salm) as required and sufficient to instruct fibrillar flight muscle fate. Without Salm, flight muscles lose their unique structural and functional properties, such as stretch-activation, resulting in viable but flightless flies.
Similar to humans Drosophila also uses a heart to pump its internal body fluid, the hemolymph. During pupal development the larval heart is remodeled and four linearly aligned heart chambers are built. We are studying adult cardiomyogenesis, in particular how the contractile filaments are assembled to enable regular and sustained heart beat.
Together with the Tomancak, Sarow and Knust labs at the MPI-CBG in Dresden we are generating a comprehensive, genome-wide set of tagged proteins within their native genomic context. We use a genome-wide FlyFos library [http://transgeneome.mpi-cbg.de/index.php?id=42] , insert GFP as well as affinity tags by recombineering, and generate transgenic flies using the integrase (attP-attB) system. We plan to generate a comprehensive transgenic resource available to the fly community.