Mechanisms regulating the maintenance of a mature skeletal musculature

• Applicant: Dr. Hanh T. Nguyen
• Subject Area: Developmental Biology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 120278921

The genetic network that controls early events in muscle formation is well characterized while little is known about the regulatory processes for stabilizing a mature skeletal musculature. We recently established that the Drosophila mind bomb 2 (mib2) gene is critical for maintaining the integrity and survival of skeletal muscles. In embryos that lack Mib2 activity, muscles are initially formed but they detach from tendon cells and degenerate during late embryogenesis. When apoptosis is inhibited, the muscle defects are less severe. Notably, mib2 function in muscles is not dependent on Notch or integrin signaling, thus invoking a novel mode of action. The goal of this proposal is to define the mechanisms through which mib2 functions to ensure the stability of the larval and adult musculatures. Specific aims are: (1) To characterize functional properties of Mib2 for maintaining muscle integrity, by performing a more detailed analysis of the mutant phenotype and defining domains that are important for mib2 function. (2) To determine the function of two novel Mib2-interacting proteins and their relationship with mib2 during larval muscle formation. (3) To analyze the functional relationships between the new Mib2- interacting proteins and Mib2 during the formation of functional and stable adult muscles.

• DFG Programme: Research Grants