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First published online 21 February 2007
doi: 10.1242/dev.000406

Development 134, 1269-1278 (2007)
Published by The Company of Biologists 2007
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Thrombospondin-mediated adhesion is essential for the formation of the myotendinous junction in Drosophila

Arul Subramanian1,*, Bess Wayburn1,*, Thomas Bunch2 and Talila Volk1,{dagger}

1 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
2 Department of Molecular/Cell Biology, University of Arizona, Tucson, AZ 85721-0001, USA.

{dagger} Author for correspondence (e-mail: lgvolk{at}weizmann.ac.il)

Accepted 23 January 2007

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.

Key words: Myotendinous junction, Thrombospondin, Integrin, Muscle, Tendon, Drosophila




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