Journal
DEVELOPMENT
Volume 147, Issue 3, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.183624
Keywords
FGF signaling; Myogenesis; Organogenesis; Myotube guidance; Rho GTPase; Actin cytoskeleton; Heartless; Drosophila embryogenesis
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Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [NIH R01AR070299]
- University of Washington Musculoskeletal Research Center [NIH P30 AR074992]
- Boettcher Foundation Webb-Waring Biomedical Research Award
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Nascent myotubes undergo a dramatic morphological transformation during myogenesis, in which the myotubes elongate over several cell diameters and are directed to the correct muscle attachment sites. Although this process of myotube guidance is essential to pattern the musculoskeletal system, the mechanisms that control myotube guidance remain poorly understood. Using transcriptomics, we found that components of the Fibroblast Growth Factor (FGF) signaling pathway were enriched in nascent myotubes in Drosophila embryos. Null mutations in the FGF receptor heartless (htl), or its ligands, caused significant myotube guidance defects. The FGF ligand Pyramus is expressed broadly in the ectoderm, and ectopic Pyramus expression disrupted muscle patterning. Mechanistically, Htl regulates the activity of Rho/Rac GTPases in nascent myotubes and effects changes in the actin cytoskeleton. FGF signals are thus essential regulators of myotube guidance that act through cytoskeletal regulatory proteins to pattern the musculoskeletal system.
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