Regulation of actin dynamics during morphogenesis and wound healing
Morphogenesis involves a complex set of cell movements. Similar cell movements are also required during the repair of damaged tissues. While cell movement has been extensively studied in culture, we currently have a relatively poor understanding of how cells move within in vivo environments and how their movements are controlled to generate complex tissues.
Our aim is to understand how cell movement in achieved and regulated during tissue morphogenesis and repair. In particular, we are interested in the role and regulation of the actin cytoskeleton during cell movement. The main model system that we use for this research is the Drosophila embryo. One advantage of using Drosophila embryos for this research is that we can readily image cell movement with high resolution in live embryos, and we have developed fluorescent probes that allow us to follow the dynamics of a range different cytoskeletal components and regulators during cell movement. A second advantage of using Drosophila is the ease with which genetic techniques can be used to dissect the function of individual genes in cell movement.
A major focus of the lab is the formation and repair of epithelial cell sheets. To investigate the formation of epithelial sheets, we study dorsal closure, a morphogenetic process in which a large hole in the epidermis of the embryo is closed. The actin cytoskeleton plays multiple roles during dorsal closure and its activity must be precisely regulated to ensure the process occurs correctly. We are particularly interested in the role and regulation of dynamic cell protrusions called filopodia that ‘stitch’ together the epidermal edges when they meet. To study the repair of epithelial sheets, we wound the epidermis of Drosophila embryos with a laser and observe the healing process in live embryos. Using a laser for wounding allows us to make very precise wounds and also allows us to observe the cellular events that occur immediately after wounding. We are interested in understanding how epithelia detect damage and how the cells surrounding the wound subsequently reorganise their actin cytoskeleton in order to become motile and thus close the wound.
In addition to investigating actin dynamics during epithelial sheet movement, we are also interested in actin dynamics during single cell movement. To study this we use haemocytes, the Drosophila equivalent of macrophages. Haemocytes undergo stereotypic migrations within the embryo, but also migrate to epidermal wounds. We can therefore use our wound model to study actin dynamics in both the epidermis and in immune cells during tissue repair.
Our research will lead to a better understanding of how cell movement is achieved and regulated within the organism, which has implications for a range for medically important processes including immune responses and tumour metastasis. In addition our work will improve our understanding of birth defects such as spina bifida and will assist in the development of therapies to improve the ability of our bodies to heal wounds.