Developmental Models for Wound Healing

Abstract

The bodies of animals and humans frequently sustain damage as a result of injury or disease, and the ability to repair this damage is essential for life. Tissue repair, or wound healing, is a complex process which is difficult to study experimentally and is, therefore, not fully understood. Over recent years, various studies have identified striking similarities between tissue repair and the process of morphogenesis in which tissues are originally formed during embryonic development. This has raised the possibility of using developmental processes as model systems to help in better understanding of tissue repair. This article describes how comparative studies of embryonic morphogenesis and tissue repair have improved understanding of the mechanisms of repair. The article further discusses the key processes and regulatory mechanisms that are shared between development and repair, including important recent developments in the field. Key Concepts: The behaviour of cells during the repair of damaged tissues often parallels that observed when tissues are initially formed during embryogenesis. Developmental processes such as Drosophila dorsal closure and mouse eyelid closure can be used as models to help in understanding of wound healing. Common cytoskeletal and signalling machineries regulate cell behaviour during the reepithelialisation episode of wound healing and also during developmental epithelial closure events. Key regulators of epithelial closure include the Rho GTPases, the JNK cascade and the planar cell polarity pathway. Coordinated collective migration of many cells is necessary for both wound healing and developmental epithelial remodelling. Mechanical signalling seems to be important for tissue remodelling, but its molecular mechanisms still largely remain elusive. Inflammatory cells play instructive roles during tissue remodelling. Novel techniques such as advanced bioimaging and mathematical modelling will help to uncover the general mechanisms underpinning wound healing and developmental tissue remodelling.

Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

“…Remodeling of AJs is essential during epithelial morphogenesis, and this remodeling is driven by the endocytosis and recycling of junction components ( Harris, 2012 ). Given the many similarities between epithelial morphogenesis and repair ( Martin and Parkhurst, 2004 ; Matsubayashi and Millard, 2013 ), we hypothesized that endocytosis-dependent remodeling of AJs is likely to also play important roles in wound healing, thus providing a possible explanation for the defective wound response observed on blocking endocytosis. To test this hypothesis, we first examined whether the remodeling of wound edge AJs to form “bulbs” at wound edge ( Figs.…”

“…Contraction of this cable pulls the wound closed in the manner of a purse string. Purse string wound closure is the primary mechanism of epithelial repair in embryonic tissues but is also believed to contribute to repair of adult tissues including the cornea and gut ( Martin and Parkhurst, 2004 ; Matsubayashi and Millard, 2013 ). Despite its widespread importance in the maintenance of epithelial tissues, the molecular mechanisms that underlie actin remodeling during wound closure remain largely unknown.…”

Analysis of the Molecular Mechanisms of Reepithelialization inDrosophilaEmbryos

“…It is relatively common for these morphogenetic events to involve a step in which two epithelial edges move toward one another and then fuse to form one continuous epithelium, a well-known example being neural tube closure in vertebrates. 33 , 34 An obvious parallel can be drawn between such processes and reepithelialization, which also involves the movement and fusion of epithelial edges. Research carried out using Drosophila embryos has revealed that this parallel is more than just superficial and that there are in fact striking similarities between wound healing and epithelial closures that occur during tissue morphogenesis.…”

“…Research carried out using Drosophila embryos has revealed that this parallel is more than just superficial and that there are in fact striking similarities between wound healing and epithelial closures that occur during tissue morphogenesis. 6 , 34 Dorsal closure is a morphogenetic event that occurs about halfway through Drosophila embryogenesis in which a large hole in the developing epidermis is closed. 35 The hole is closed by the movement of two sheets of epidermal cells toward one another until the leading edges of the two sheets meet and fuse ( Fig.…”