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This study investigated which adherens junction proteins, typically associated with epithelial cell adhesion, play roles in mesenchymal cell migration using developing Drosophila testis as a model system. The researchers combined a mammalian proximity proteomics dataset with genome-wide shRNA screening in Drosophila, discovering that several proteins considered critical in epithelial contexts, such as Canoe, Polychaetoid, and Bazooka, have only modest roles in mesenchymal migration. Notably, the kinase Par-1 was found to regulate cell migration and gap closure in a manner resembling myosin function, while the Rab GAP RN-tre acts after migration to influence testis spiralization in parallel with N-cadherin.
Why it matters
Understanding which adhesion-related proteins drive mesenchymal migration is relevant to fields such as developmental biology, wound healing, and cancer metastasis, where collective cell movement plays a central role. The 22 identified candidate genes represent a resource that could guide future research into the molecular mechanisms underlying tissue morphogenesis and potentially inform therapeutic strategies targeting aberrant cell migration.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Animal tissues have diverse architectures and cell behaviors across the epithelial-mesenchymal spectrum. Cell adhesion mediated by classical cadherins is foundational. Cadherins nucleate complexes of dozens of proteins connecting junctions to the cytoskeleton and signaling downstream. Many junctional proteins are well-studied in epithelia, but less is known about roles during mesenchymal migration. The nascent myotubes of the pupal Drosophila testis provide an excellent model for N-cadherin mediated mesenchymal migration. We combined a proximity proteomics dataset of adherens junction proteins in mammalian epithelial cells with genome-wide shRNA libraries knocking down Drosophila genes to begin to define the subset of junctional proteins important in mesenchymal migration. While N-cadherin is predominant, E-cadherin plays a supporting role. Surprisingly, several proteins with key roles in epithelial morphogenesis, including Afadins homolog Canoe, ZO-1s homolog Polychaetoid, and Par3s homolog Bazooka play at most modest roles. Twenty-two genes with diverse cell biological roles had strong to moderate defects in testis morphogenesis. These will provide a community resource. We followed up two. The kinase Par-1 is important for migration and gap closure, with knockdown phenotypes paralleling those of myosin. The Rab GAP RN-tre does not have roles until after migration and works in parallel with N-cadherin during testis spiralization.