Our ability to understand the morphogenesis defects underlying hereditary ocular malformations such as cyclopia and micro/anophthalmia depends upon having a good understanding of the cellular events leading to the separation of the optic vesicles (OVs). The primordium of the eyes is specified as a single domain within the neural plate, which subsequently splits in two primordia, the OVs. Despite significant advance in the last few years to identify the main signals and transcription factors required for early eye development, we have a very limited knowledge about the cell behaviour involved in OV evagination, the signals that regulate this behaviour, and how defects in them might lead to eye morphogenesis phenotypes including cyclopia or micro/anophthalmia. In this proposal, we will make use of advanced imaging techniques in the living fish embryo to follow cell behaviour and analyse the impact of cell polarity establishment and adhesion properties during eye morphogenesis. Our preliminary analyses suggest that the Wnt and Ephrin signalling pathways may have important roles during OV evagination. We will manipulate the activity of these pathways and analyse how this affects cell behaviour, polarity and adhesion during eye morphogenesis. We will combine in vivo and in vitro approaches in a program of research that will help us analyse whether the dynamic behaviour of eye cells may be an intrinsic property of these cells, or may require their interaction with the surrounding tissues. We anticipate that this programme of research will make major contributions to our understanding of early eye morphogenesis and will set the basis to understand how defects in cell behaviour may lead to absence of optic vesicle evagination in cyclopia and micro/anophthalmia associated conditions.
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