Microtubule (MT)-dependent regulation of muscle length. Victoria K. Schulman^1,2, Eric S. Folker², Mary K. Baylies^1,2. 1) Weill Cornell Graduate School of Medical Sciences, New York, NY; 2) Sloan-Kettering Institute, New York, NY.

   Many muscle diseases are characterized by smaller, weaker myofibers, highlighting the fact that muscle size is critical for muscle function. To study the regulation of muscle size, we used the model organism, Drosophila melanogaster, a system that permits in vivo cell biological studies with an additional means to assess muscle function at later stages of development. Many aspects of morphogenesis determine overall muscle size, including nuclear number, cell volume, and myofiber length. We have focused on how muscle length is regulated because we have shown that larvae with shorter muscles exhibit significantly impaired muscle function. Through a combination of mutational analysis and RNAi-based screens, we have identified a number of factors that affect muscle length. Mutations in, or depletion of, Lis1, NudC, Rapsynoid (Raps/Pins), the minus-end directed MT motor Dynein heavy chain (Dhc), and its regulatory light chain (Dlc), all result in muscles that are shorter than controls. Conversely, mutations in, or depletion of, the plus-end directed motor Kinesin heavy chain (Khc), its regulatory light chain (Klc), and Ensconsin (Ens), exhibit significantly longer muscles compared to controls. Finally, we have identified Sunday Driver (Syd) as a factor that coordinates Kinesin and Dynein activities as they pertain to muscle length determination. Although homozygous syd mutants produce muscles of the proper length, double heterozygotes of syd and khc have longer muscles than controls, and double heterozygotes of syd and dhc have shorter muscles than controls. This suggests that the adapter protein, Syd, is simultaneously regulating Dhc and Khc to influence muscle length. Collectively, these data suggest that muscle length is regulated by a MT-dependent process mediated by motor protein complexes that are coordinated by Syd to facilitate proper extension of the muscle pole.