Analysis of the Molecular Mechanisms of Reepithelialization inDrosophilaEmbryos

Abstract

Significance: The epidermis provides the main barrier function of skin, and therefore its repair following wounding is an essential component of wound healing. Repair of the epidermis, also known as reepithelialization, occurs by collective migration of epithelial cells from around the wound edge across the wound until the advancing edges meet and fuse. Therapeutic manipulation of this process could potentially be used to accelerate wound healing.Recent Advances: It is difficult to analyze the cellular and molecular mechanisms of reepithelialization in human tissue, so a variety of model organisms have been used to improve our understanding of the process. One model system that has been especially useful is the embryo of the fruit fly Drosophila, which provides a simple, accessible model of the epidermis and can be manipulated genetically, allowing detailed analysis of reepithelialization at the molecular level. This review will highlight the key insights that have been gained from studying reepithelialization in Drosophila embryos.Critical Issues: Slow reepithelialization increases the risk of wounds becoming infected and ulcerous; therefore, the development of therapies to accelerate or enhance the process would be a great clinical advance. Improving our understanding of the molecular mechanisms that underlie reepithelialization will help in the development of such therapies.Future Directions: Research in Drosophila embryos has identified a variety of genes and proteins involved in triggering and driving reepithelialization, many of which are conserved in humans. These novel reepithelialization proteins are potential therapeutic targets and therefore findings obtained in Drosophila may ultimately lead to significant clinical advances.

Multiple Mechanisms Drive Calcium Signal Dynamics around Laser-Induced Epithelial Wounds

“…Epithelial wound healing is a multistage process. Cells must detect the presence of a wound, migrate and proliferate in a coordinated fashion to close the defect, and then successfully reestablish tissue-wide epithelial architecture (1)(2)(3)(4)(5). An important early feature of the wound response is a rapid rise in cytosolic calcium.…”

In vivo imaging of epithelial wound healing in the cnidarian Clytia hemisphaerica demonstrates early evolution of purse string and cell crawling closure mechanisms

“…From studies in all these systems, the consensus has emerged that there are two distinct sequences of events that can close epithelial gaps 1) Lamellipodia-dependent cell crawling - Lamellipodia are produced by cells adjacent to the wound (marginal cells) and these cells migrate into the gap; in large wounds, cells behind the marginal cells migrate as well; 2) “Purse string” closure- Actin filaments associated with myosin II form a super-cellular cable around the wound circumference, presumably linking cells through adherens junctions. This cable contracts, drawing the edges of marginal cells inwards [ 1 , 2 , 8 , 11 , 14 – 19 ] . In either mechanism, the edges of the cells eventually meet across the shrinking gap and establish junctions to restore the integrity of the epithelial cell sheet.…”

Gradual specialization of phagocytic ameboid cells may have impaired regenerative capacities in metazoan lineages

“…81 In addition, these PACs participate in epidermal wound-healing 82,83 but not in the subsequent phases of regeneration because the ablation of these cells during larval stages of Drosophila melanogaster has been shown to not prevent the regeneration of the imaginal disc. 84 Re-epithelization is important to block leakage of body fluids and the entry of pathogens 85 (Figure 2), a clear cytotoxic behavior compatible with early stages of tissue repair. 86 Arthropod PACs are generated from specific body compartments through hematopoiesis and are more related to mammalian PACs.…”

“…Re‐epithelization is important to block leakage of body fluids and the entry of pathogens 85 (Figure 2), a clear cytotoxic behavior compatible with early stages of tissue repair 86 …”