Thrombospondin-mediated adhesion is essential for the formation of the myotendinous junction in Drosophila.
Organogenesis of the somatic musculature in Drosophila is directed by the precise adhesion between migrating myotubes and their corresponding ectodermally derived tendon cells. Whereas the PS integrins mediate the adhesion between these two cell types, their extracellular matrix (ECM) ligands have been only partially characterized. We show that the ECM protein Thrombospondin (Tsp), produced by tendon cells, is essential for the formation of the integrin-mediated myotendinous junction. Tsp expression is induced by the tendon-specific transcription factor Stripe, and accumulates at the myotendinous junction following the association between the muscle and the tendon cell. In tsp mutant embryos, migrating somatic muscles fail to attach to tendon cells and often form hemiadherens junctions with their neighboring muscle cells, resulting in nonfunctional somatic musculature. Talin accumulation at the cytoplasmic faces of the muscles and tendons is greatly reduced, implicating Tsp as a potential integrin ligand. Consistently, purified Tsp C-terminal domain polypeptide mediates spreading of PS2 integrin-expressing S2 cells in a KGD- and PS2-integrin-dependent manner. We propose a model in which the myotendinous junction is formed by the specific association of Tsp with multiple muscle-specific PS2 integrin receptors and a subsequent consolidation of the junction by enhanced tendon-specific production of Tsp secreted into the junctional space.
Subramanian
Arul
A
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Wayburn
Bess
B
Bunch
Thomas
T
Volk
Talila
T
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D039001:Integrin alpha Chains / Q000378:metabolism; D008954:Models, Biological; D009132:Muscles / Q000196:embryology*; D013710:Tendons / Q000196:embryology* / Q000378:metabolism; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D039001:Integrin alpha Chains; D019699:Thrombospondins; D014157:Transcription Factors; C082188:if protein, Drosophila; C096359:sr protein, Drosophila