Identification of novel regulators of epithelial closure (360G-Wellcome-211808_Z_18_Z)

Epithelial closure is a process that is frequently used to close holes or gaps in epithelial sheets. The process can be observed during wound healing and multiple morphogenetic events. The fusion of the epithelial sheets is co-ordinated by the cells at the leading edge of the sheets. These cells create dynamic actin protrusions that recognise and pair with the protrusions from the opposing sheet, and join the sheets together in a 'zippering' process. Correct alignment of the sheets is crucial to ensure that the fusion is accurate. The actions and signalling of the leading edge cells is influenced by the Jun N-terminal kinase (JNK) pathway. This pathway is known to regulates multiple genes, but its exact impact on the events occurring in leading edge is still unknown. In this project we alter the levels of selected JNK target genes and observe how this affects epithelial closure. This is done by fluorescence imaging of live and fixed Drosophila embryos during dorsal closure. The aim is to identify the key regulatory proteins and determine how they control actin protrusions on the leading edge. This research will further our understanding of the events during epithelial closure, and has applications in treating developmental defects.