Résumé :
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Our aim is to understand how skeletal muscle form and grow during vertebrate embryonic development. The early skeletal muscle (the primary myotome, composed of mononucleated, post-mitotic muscle fibers, the myocytes) is formed from the generation of muscle cells at the four borders of the dermomyotome, the dorsal-most epithelial compartment of somites. Most of the dermomyotome undergoes an epithelial to mesenchymal transition that leads to the emergence of a population of resident muscle progenitors that massively contributes to the growth of all trunk muscles. The medial border of the dermomyotome (DML) remains epithelial for a considerable period of time, during which it generates muscle cells that contribute to the growth of the primary myotome. DML stem/progenitor cells can adopt two fates during the first days of embryonic muscle development: to self-renew and remain in the epithelial border of the dermomyotome or to translocate in the myotome and undergo terminal myogenic differentiation. How this balance is regulated is unknown. We show that muscle progenitors present in the DML require the transient activation of NOTCH signaling to undergo terminal differentiation. The NOTCH ligand Delta1 is expressed in a mosaic pattern in neural crest cells that migrate past the somites. Gain and loss of Delta1 function in neural crest modifies NOTCH signaling in somites, which results in delayed or premature myogenesis. Our results suggest that the neural crest regulates early muscle formation by a unique mechanism that relies on the migration of Delta1-expressing neural crest cells to trigger the transient activation of NOTCH signaling in selected muscle progenitors. This dynamic signaling guarantees a balanced and progressive differentiation of the muscle progenitor pool.
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