The function of Drosophila Integrin-Dim7-Elmo-Mbc→Rac signaling pathway in the muscle attachment formation and maintenance
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The Engulfment and Cell Motility (Elmo)-(Myoblast city) Mbc→Rac signaling pathway is evolutionarily conserved from C. elegans to vertebrates and is essential for many developmental processes, including phagocytosis and cell migration. Flies that possess mutations in the elmo locus are lethal and exhibit defects in myoblast fusion, thorax closure, and border cell migration. Herein, using mass spectrometry approaches to identify new players in the Elmo signaling pathway, we uncovered Drosophila Importin-7 (Dim7), encoded by moleskin (msk), as a potential Elmo-interacting protein. In msk mutants, which exhibit muscle detachment phenotypes, the tendon cell differentiation factors Stripe or activated Mitogen-activated kinase (pMAPK) are missing from the tendon cells. Our data shows that Msk signals from the muscle cell via the secreted Epidermal growth factor receptor (Egfr) ligand Vein to regulate tendon cell maturation. In the muscle, Dim7 acts upstream to recruit the Elmo-Mbc signaling module to the ends of muscles for stable muscle attachments. Both Dim7 and Elmo are localized to the muscle attachment sites (MASs) during myogenesis, and phenotypic analysis of elmo mutants show muscle attachment defects as that of previously described in msk. The muscle detachment phenotype in msk mutants can be rescued by components in the Elmo-signaling pathway, including the Elmo-Mbc complex, an activated Elmo variant, or constitutively active Rac. In actively contracting larval muscles, integrins function as upstream signals to mediate Dim7-Elmo enrichment to the MASs. We postulate that the regulation of Rac activity at the ends of muscles locally modulates the internal actin cytoskeleton to maintain stable muscle attachments during muscle growth or in response to changes in force transmission in active muscle contraction.
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General introduction -- Methodology -- Part I. Drosophila moleskin is essential for the formation of the stable muscle attachment -- Part. II. Drosophila importin-7 functions upstream of the elmo-signaling module to mediate the formation and stability of muscle attachment
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Ph.D.