The dPix-Git complex is essential to coordinate epithelial morphogenesis and regulate myosin during Drosophila egg chamber development

摘要

How biochemical and mechanical information are integrated during tissue development is a central question in morphogenesis. In many biological systems, the PIX-GIT complex localises to focal adhesions and integrates both physical and chemical information. We used Drosophila melanogaster egg chamber formation to study the function of PIX and GIT orthologues (dPix and Git, respectively), and discovered a central role for this complex in controlling myosin activity and epithelial monolayering. We found that Git’s focal adhesion targeting domain mediates basal localisation of this complex to filament structures and the leading edge of migrating cells. In the absence of dpix and git , tissue disruption is driven by contractile forces, as reduction of myosin activators restores egg production and morphology. Further, dpix and git mutant eggs closely phenocopy defects previously reported in pak mutant epithelia. Together, these results indicate that the dPix-Git complex controls egg chamber morphogenesis by controlling myosin contractility and Pak kinase downstream of focal adhesions. Author summary A major challenge in biology is to identify the genes and processes that build tissues of correct shape and function. Recently, transmission of mechanical forces through cell adhesions, and control of cell tension via contractile force-generating proteins, have emerged as fundamental to tissue development. Currently, we do not understand how these separate processes are integrated. We gained new insight into morphogenesis and control of contraction through adhesion-localised proteins, by studying mutants of the dPix-Git focal adhesion complex in Drosophila melanogaster egg chambers, a 3D model of tissue morphogenesis. We found that the dPix-Git complex is essential to maintain cell monolayers, and is a regulator of the contractile force-generating protein, myosin. In the absence of the dPix-Git complex, irregular myosin activation led to tissue disruption, however modest suppression of myosin activators rescued this defect. Remarkably, the dPix-Git complex is essential for egg chamber development, but appears dispensable for other D . melanogaster epithelia, indicating the mechanisms that couple adhesion signalling and cell contractile forces are tissue specific. Our study reveals a key molecular link between cell adhesions and contraction, and the conservation of the dPix-Git module in metazoans suggests this mechanism is likely to be evolutionarily conserved in other tube-like tissues.