AlphaPS2 integrin-mediated muscle attachment in Drosophila requires the ECM protein Thrombospondin.
During Drosophila embryogenesis, the attachment of somatic muscles to epidermal tendon cells requires heterodimeric PS-integrin proteins (alpha- and beta-subunits). The alpha-subunits are expressed complementarily, either tendon cell- or muscle-specific, whereas the beta-integrin subunit is expressed in both tissues. Mutations of beta-integrin cause a severe muscle detachment phenotype, whereas alpha-subunit mutations have weaker or only larval muscle detachment phenotypes. Furthermore, mutations of extracellular matrix (ECM) proteins known to act as integrin binding partners have comparatively weak effects only, suggesting the presence of additional integrin binding ECM proteins required for proper muscle attachment. Here, we report that mutations in the Drosophila gene thrombospondin (tsp) cause embryonic muscle detachment. tsp is specifically expressed in both developing and mature epidermal tendon cells. Its initial expression in segment border cells, the tendon precursors, is under the control of hedgehog-dependent signaling, whereas tsp expression in differentiated tendon cells depends on the transcription factor encoded by stripe. In the absence of tsp activity, no aspect of muscle pattern formation as well as the initial contact between muscle and tendon cells nor muscle-to-muscle attachments are affected. However, when muscle contractions occur during late embryogenesis, muscles detach from the tendon cells. The Tsp protein is localized to the tendon cell ECM where muscles attach. Genetic interaction studies indicate that Tsp specifically interacts with the alphaPS2 integrin and that this interaction is needed to withstand the forces of muscle contractions at the tendon cells.
Chanana
Bhavna
B
Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, 37077 Göttingen, Germany.
Graf
Roland
R
Koledachkina
Tatyana
T
Pflanz
Ralf
R
Vorbrüggen
Gerd
G
D000818:Animals; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D000078404:Epidermal Cells; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D039001:Integrin alpha Chains / Q000378:metabolism*; D009119:Muscle Contraction; D009132:Muscles / Q000196:embryology* / Q000378:metabolism; D009154:Mutation; D013710:Tendons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D019699:Thrombospondins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D039001:Integrin alpha Chains; D019699:Thrombospondins; C082188:if protein, Drosophila