Cell wounding is a common event in the life of many cell types, and the capacity of the cell to repair day-to-day wear-and-tear injuries, as well as traumatic ones, is fundamental for maintaining tissue integrity. By taking in molecular debris along the periphery of wounded cells, unwounded cells give themselves the room they need to wriggle into and stretch over wounded areas in embryonic tissue. This ground-clearing approach to wound healing was observed in fruit flies by means of in vivo time-lapse quantitative microscopy. Close examination of fruit fly embryos also led to the identification of factors that keep the endocytic machinery moving (or not), expediting (or slowing) wound healing.
These results were reported by a research team composed of scientists from the University of Toronto and the Hospital for Sick Children. According to this team, the study of wound repair mechanisms in fruit fly embryos could suggest ways to improve wound recovery in humans.
“Wounds in embryos heal very quickly and with very little inflammation or scarring,” said Miranda Hunter, a Ph.D. candidate at the University of Toronto and lead author of the research team’s study, which appeared August 31 in the Journal of Cell Biology (JBC). “Our hope is that by understanding how embryos repair wounds, we can translate our understanding into more efficient treatments to induce adult cells to move into the wound area in a coordinated way as embryonic cells do.”
The new study—“Polarized E-cadherin endocytosis directs actomyosin remodeling during embryonic wound repair”—describes how the endocytic machinery works. Besides coordinating the removal of cellular debris, this machinery directs the formation of a structure known as a “purse string,” a structure that assembles around the wound and rapidly contracts to draw surrounding cells together and close a wound.
“We … show that clathrin, dynamin, and the ADP-ribosylation factor 6, three components of the endocytic machinery, accumulate around wounds in Drosophila melanogaster embryos in a process that requires calcium signaling and actomyosin contractility,” wrote the authors of the JBC article. “Blocking endocytosis with pharmacological or genetic approaches disrupted wound repair. The defect in wound closure was accompanied by impaired removal of E-cadherin from the wound edge and defective actomyosin cable assembly.”
The authors also observed that E-cadherin overexpression resulted in reduced actin accumulation around wounds and slower wound closure. This observation prompted the investigators to try reducing E-cadherin levels in embryos in which endocytosis was blocked. After this intervention, the investigators found, actin localization to the wound margin was rescued.
The research team’s leader, Rodrigo Fernandez-Gonzalez, Ph.D., is affiliated with both the University of Toronto and the Hospital for Sick Children. He noted that his team’s study opens up a range of possibilities: “It shows how cells move in a coordinated manner, which helps us to understand more about processes such as cancer metastasis and embryonic development.”