Research SummaryReceptor tyrosine kinase signaling in skeletal muscle development, regeneration and disease
Receptor tyrosine kinases (RTKs) comprise a family of cell surface receptors that mediate signaling cascades critical to cellular processes such as survival, proliferation, differentiation and migration. These processes in turn are essential for organ morphogenesis, embryonic development and tissue homeostasis. Previous studies have shown that RTKs crucial for developmental morphogenesis are also dysregulated in pathological states. For example the RTKs -FGFR3 and c-KIT play crucial roles during development and mutations in these genes cause the developmental disorders dwarfism and piebaldism. Interestingly, aberrant signaling from these RTKs cause bladder cancer and gastrointestinal stromal tumors respectively. Similarly, signaling through the RTK MET is vital during developmental skeletal myogenesis, and adult muscle regeneration; MET is also known to be dysregulated in Rhabdomyosarcoma, a cancer related to the myogenic lineage. Since, MET signaling is crucial to skeletal muscle development and regeneration, it is important to determine the mechanisms underlying its regulation that have remained largely unexplored. My aim is to understand the specific spatial and temporal regulation of this signaling pathway in skeletal muscle development, regeneration and disease using mouse as in vivo model and myogenic cells as in vitro tool. The proposed work will provide important insights into regulation of skeletal muscle development and regeneration, which could potentially aid therapy in muscle diseases such as Duchenne muscular dystrophy and muscle atrophy during ageing.
Figure Legend: Confocal image showing alveolar rhabdomyosarcoma cells labeled by immunofluorescence for MET (red), phalloidin (green) marking the actin filaments and DAPI (blue) staining the nuclei.