Mechanisms of neural tube closure

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Neural tube closure is a morphogenetic process that involves complex behaviors of polarized neural plate cells. With more than 200 genes implicated in this process in genetic models, neural tube abnormalities are among the most common human birth defects. Nevertheless, mechanisms of neural tube closure remain poorly understood and the available vertebrate models are limited. Our preliminary experiments have identified a unique polarization of several proteins in the plane of the Xenopus neural plate and demonstrated that this polarity requires the functions of both planar cell polarity (PCP) and apical-basal polarity proteins. The proposed studies will carry out live imaging of the neural plate using a novel fluorescent sensor. New molecules that physically associate with the PCP complex will be identified using a novel proximity- and complementation- based biotinylation approach combined with mass spectrometry. The involvement of the apical-basal polarity proteins in PCP signaling during neural tube closure will also be evaluated. Xenopus embryos are easily accessible at any developmental stage and are uniquely suited for these studies, allowing rapid analysis of protein localization and function through a combination of biochemical, embryological and cell biological approaches. These experiments will shed light on basic signaling mechanisms that underlie normal development of the central nervous system. The proposed studies are highly relevant to human health, because misregulation of these signaling pathways leads to brain and neural tube defects and a variety of neurological disorders.   .