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We are interested in deciphering the mechanisms underlying mammalian embryonic development, stem cell mediated regeneration and diseases associated with abnormal development and regeneration. The cells in the developing embryo or regenerating tissues undergo processes such as specification, migration, proliferation, differentiation and apoptosis in a coordinated manner. We are trying to understand the signals controlling these cellular processes and their regulation. During the process of differentiation, cells undergo changes in morphology and cellular activity, based on their lineage and functional requirements. This is best illustrated in the case of the mammalian skeletal muscle, where the undifferentiated stem cells are small, round and mononuclear, whereas the mature, differentiated cells are large, elongated and multinuclear. One gene family crucial to skeletal muscle differentiation are the skeletal muscle myosin heavy chains, expressed specifically by the skeletal muscle, with different members expressed at different developmental stages, adult life, and during muscle injury or disease. One such myosin heavy chain is myosin heavy chain-embryonic, encoded by the Myh3 gene. By generating knockout mice lacking Myh3 and employing mouse genetics, we have characterized the embryonic and perinatal functions of myosin heavy chain-embryonic in the skeletal muscle (Agarwal et al, Development 2020). Mutations in specific myosins have been reported to cause congenital diseases such as contracture syndromes, myopathies etc, and our studies using mouse models should lead to a mechanistic understanding of these diseases and possible therapeutic strategies to treat them.
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