Epithelia have the essential role of acting as a barrier that protects living organisms and its organs from the surrounding milieu. Therefore, it is crucial for epithelial tissues to have robust ways of maintaining its integrity despite the frequent damage caused by normal cell turnover, inflammation and injury. All epithelia have some capacity to repair themselves, however, the wound-healing process differs dramatically between the developmental stage and type of tissue involved. In this project we will focus on investigating the capacity that several simple epithelial tissues have to reseal small discontinuities very rapidly and efficiently. This repair mechanism that we call epithelial resealing is based on the contraction of an actomyosin purse string in the leading edge cells around the wound margin. Epithelial resealing seems to be a fundamental repair mechanism, acting in several types of simple embryonic and adult epithelia, in both vertebrates and invertebrates. The cell biology of epithelial resealing has started to be understood but there are still many open questions and the signalling cascades that regulate this process are largely unknown. We propose to investigate epithelial resealing using a combination of genetics and high resolution live imaging. The Drosophila embryonic epithelium will be our primary model system and we will start by characterizing in detail novel genes involved in resealing that have been identified in a pilot screen previously performed in the laboratory. We will also perform a new RNAi genetic screen based on a very large collections of transgenic lines to completely unravel the signalling network that controls epithelial resealing. In order to investigate how conserved in vertebrates are the epithelial resealing mechanisms, we will establish epithelial wounding assays in zebrafish simple epithelial tissues and we will study, in this vertebrate model system, the molecular mechanisms that we will uncover using Drosophila.