Research Projects

Skeletal muscle differentiation is the process where progenitor cells become mature muscle fibers, regulated by factors such as growth factors, myogenic regulatory factors (MRFs), myocyte-enhancing factors (MEFs), tissue-specific splicing factors, cell-signalling molecules, and long noncoding RNAs. Deregulation of muscle differentiation programs is common in muscular disorders, where effective treatment is limited. Understanding normal muscle differentiation at the molecular level is crucial for understanding differentiation defects and developing better therapeutics. Wnt signaling occurs through ?-catenin dependent (canonical) or independent (noncanonical) pathways. Canonical Wnt signaling regulates the differentiation of muscle satellite cells, while noncanonical signals are involved in the self-renewal of satellite stem cells and muscle growth. However, the molecular details of how noncanonical Wnt pathway mediates skeletal muscle differentiation are largely unknown. This study aims to understand the role of Wnt7b-induced noncanonical in skeletal muscle differentiation. The study will analyze the expression level of Wnt7b during skeletal muscle differentiation and its subcellular localization, and use depletion and/or ectopic expression studies to understand its role in muscle differentiation. The study will also explore the role of various functional domains of Wnt7b necessary to induce skeletal muscle differentiation. The proposed objectives are designed to be implemented in parallel and completed within three years. Completion of this proposal will provide a clear understanding of Wnt7b's role in muscle differentiation, its regulation of muscle-specific gene expression programs, and novel Wnt7b upstream/downstream effectors necessary for myogenic programs.