Plexins function in epithelial repair in both Drosophila and zebrafish.

Sa Kan Yoo,Heath G Pascoe,Telmo Pereira,Xuewu Zhang,Iswar K Hariharan,Shu Kondo,Antonio Jacinto

doi:10.1038/ncomms12282

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.

Highlights

In most multicellular organisms, homeostasis is contingent upon maintaining epithelial integrity
In the vicinity of the wound, we observed a rapid increase immediately after wounding, which persisted for 5–10 min (Fig. 1b and Supplementary Movie 2), which is similar to the wound-induced calcium flashes observed in the Caenorhabditis. elegans epidermis[9], the zebrafish tail fin[2] and the Drosophila embryonic and pupal epithelia[10,11]
We have described a role for Drosophila PlexA and for its zebrafish orthologue Plexin A1 in wound repair

Summary

Introduction

Homeostasis is contingent upon maintaining epithelial integrity. We describe a role for Plexin A (PlexA), a protein with well-characterized roles in axonal pathfinding, in the healing of damaged epithelia in Drosophila. Our observations suggest that the inhibition of Rap[1] activity by PlexA in damaged Drosophila epithelia allows epithelial remodelling, facilitating wound repair. We first screened for regulators of wound repair in Drosophila imaginal discs and tested whether the orthologous genes in zebrafish have a similar function. Using this approach, we have identified a key role for plexins during tissue repair in both organisms

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Conclusion