Crawling wounded: molecular genetic insights into wound healing from Drosophila larvae

Abstract

For animals, injury is inevitable. Because of this, organisms possess efficient wound healing mechanisms that can repair damaged tissues. However, the molecular and genetic mechanisms by which epidermal repair is accomplished remain poorly defined. Drosophila has become a valuable model to study epidermal wound healing because of the comprehensive genetic toolkit available in this organism and the similarities of wound healing processes between Drosophila and vertebrates. Other reviews in this Special Issue cover wound healing assays and pathways in Drosophila embryos, pupae and adults, as well as regenerative processes that occur in tissues such as imaginal discs and the gut. In this review, we will focus on the molecular/genetic control of wound-induced cellular processes such as inflammation, cell migration and epithelial cell-cell fusion in Drosophila larvae. We will give a brief overview of the three wounding assays, pinch, puncture, and laser ablation, and the cellular responses that ensue following wounding. We will highlight the actin regulators, signaling pathways and transcriptional mediators found so far to be involved in larval epidermal wound closure and what is known about how they act. We will also discuss wound-induced epidermal cell-cell fusion and possible directions for future research in this exciting system.

Fig. 1.. Methods used to wound Drosophila larvae.

(A) Cartoons of the different wounding procedures. (B) Schematics of the larval epithelia after wounding. Membranes, green; Nuclei, red. White dashed lines indicate the wound edge. (C) Details of size, sterility, inflammation, optimal uses, and primary references.

Fig. 2.. Signaling pathways that regulate cellular responses in wound-edge cells.

(A) Cartoon of transverse view of a wound edge larval epidermal cell annotated with cellular structures and functions of wound healing pathways. (B) Cartoon of top-down view of a wound edge larval epidermal cell. Receptors and ligands that affect pinch wounding are illustrated as are selected pathway components, in particular transcription factors and target genes that regulate actin. Double-headed red arrow indicates the genetic interaction between JNK and yki signaling. Other pathway interactions or lack thereof are addressed in the text. Asterisk: proteins that show translocation after wounding. (C) Table summarizing wound healing pathway functions, signals, and transcription factors, if known. The role of insulin signaling in healing of multicellular wounds is not yet clear and is not depicted here-please refer to the section on insulin signaling for its roles in single cell healing in the larval epidermis.

Fig. 3.. Wound-edge epidermal cell processes possess a basal lamina along their entire length.

A transverse section of a whole-mount epidermis eight hours after wounding under transmission electron microscopy. The basal side of the thin process contains a basal lamina (arrowheads) to the end of the extension (arrow). ep, epidermal process; c, cuticle; d, wound site debris; p, plasmatocyte. Scale bar, 2 μm.