Regulation of Sarcomere Growth

PROJECT SUMMARY/ABSTRACT It is well established that the addition or removal of sarcomeres is central in determining muscle size and force output during normal development, but also in response to mechanical stimuli or pathological conditions. Overstretched muscle can initiate new sarcomere formation, while chronic understretching reduces sarcomere number and may shorten muscle lengths. Other than disease states or mechanical-load induced alterations, few studies have examined force-independent factors that influence skeletal muscle sarcomere remodeling. Moreover, a major knowledge gap is understanding how muscle-intrinsic factors contribute to sarcomere addition during muscle growth. To address these deficiencies, we have established genetic backgrounds that promote larval muscle growth to quantitatively study serial sarcomere addition at a single-cell resolution in the experimentally tractable Drosophila model. Completion of the following two aims will help us accomplish our long-term goal of understanding how muscle length increases at both the sarcomere and whole tissue levels during development and growth. Aim 1 will determine the identity of molecular targets that impact sarcomere addition using transcriptomic and candidate approaches. Aim 2 will use in vivo protein tagging methods to follow the fate of newly synthesized sarcomere proteins during muscle growth. We expect that this project will fundamentally advance our understanding of signaling pathways required for sarcomere addition and will establish new techniques for studying sarcomere dynamics.