Endocrine Abstracts

Embryos heal wounds very rapidly and efficiently and without leaving a scar. Studying how they do this can tell us much about the natural morphogenetic movements of embryogenesis as well as suggesting ways in which we might make adult tissues repair more efficiently. Using live confocal imaging of transgenic Drosophila embryos expressing gfp-actin in epithelial tissues we have revealed the key actin machineries that drive the paradigm morphogenetic process of dorsal closure which appears to bear striking analogy with re-epithelialisation of a vertebrate skin wound. Using embryos expressing mutant forms of the various small GTPases, we have tested the function of each of these actin-based elements (the actin cable and dynamic filopodia and lamellipodia) in both dorsal closure and the repair of laser-generated wound holes. Our experiments in embryonic chicks and mice and in the neonatal PU.1 null mouse, which is genetically macrophageless, suggest that an inflammatory response is not essential for repair and may indeed be causal of fibrosis in post-embryonic animals. Consequently, we have used a microarray approach with this mouse in order to identify a portfolio of candidate inflammation/fibrosis genes. Finally, we have established models of inflammation in the Drosophila embryo and in the translucent zebrafish larval tail, which allow us to make DIC movies of the inflammatory response and to dissect the genetics of inflammation, including the precise roles of each of the small GTPases in recruitment of inflammatory cells to the wound site.