Plexins function in epithelial repair in both Drosophila and zebrafish

Abstract

In most multicellular organisms, homeostasis is contingent upon maintaining epithelial integrity. When unanticipated insults breach epithelial barriers, dormant programmes of tissue repair are immediately activated. However, many of the mechanisms that repair damaged epithelia remain poorly characterized. Here we describe a role for Plexin A (PlexA), a protein with particularly well-characterized roles in axonal pathfinding, in the healing of damaged epithelia in Drosophila. Semaphorins, which are PlexA ligands, also regulate tissue repair. We show that Drosophila PlexA has GAP activity for the Rap1 GTPase, which is known to regulate the stability of adherens junctions. Our observations suggest that the inhibition of Rap1 activity by PlexA in damaged Drosophila epithelia allows epithelial remodelling, thus facilitating wound repair. We also demonstrate a role for Plexin A1, a zebrafish orthologue of Drosophila PlexA, in epithelial repair in zebrafish tail fins. Thus, plexins function in epithelial wound healing in diverse taxa.

Cell Extrusion: A Stress-Responsive Force for Good or Evil in Epithelial Homeostasis

“…Cell-cell communication mechanisms may therefore be broadly conserved between neuroepithelial progeny, with typically repulsive axon-guidance genes functioning in epithelia to extrude aberrant cells. Indeed, alongside Slit-Robo, ephrin-A-EphA2 signaling repels and extrudes Ras V12 cells in MDCK monolayers and wing discs (Porazinski et al, 2016), and repulsive Semaphorin-Plexin signaling removes damaged cells by basal extrusion during JNK-dependent wound healing in wing discs (Yoo et al, 2016). As JNK signaling is required for diverse phenomena that include cell extrusion, such as cell competition and wound healing, downstream signals like Slit-Robo and subsequent junctional dissolution may more broadly mediate cell extrusion and regulate epithelial homeostasis.…”

Slit-Robo Repulsive Signaling Extrudes Tumorigenic Cells from Epithelia

“…Different JNK-activated actin regulators may therefore prevent or promote tumorigenesis depending on the tumor’s genetic context. Intriguingly, a recent study further connected JNK-dependent cell movement with axon-guidance genes: repulsive Semaphorin-Plexin signaling mediated epithelial wound repair, which is a dynamic and JNK-dependent process (Yoo et al, 2016). Thus, canonical “axon-guidance” signals may mediate manifold forms of cell-cell communication and movement.…”

Imaginal disc regeneration takes flight

“…Functional screens for genes that regulate the early stages of wound healing in Drosophila imaginal discs are only beginning, and one such screen demonstrated a role for Plexin A in the repair of wounds in imaginal discs [46]. Since plexins and semaphorins, which have known functions in axonal pathfinding, predate the evolution of the nervous system, it is possible that the ancestral function of this pathway is to repair damaged epithelia.…”