Roles and mechanisms of asymmetric LRP6 localization in Xenopus embryonic cells

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LRP6 is a Wnt coreceptor which plays a key role in transducing b-catenin signaling. Our unpublished data show that LRP6 is asymmetrically distributed in Xenopus ectodermal cells, where it is localized in the basolateral- and is depleted in the apical domains. This distribution may be physiologically relevant since daughter cells preferentially inheriting the basolateral and apical membranes display high and low Wnt/b-catenin signaling, respectively. We therefore propose to study the regulation of LRP6 embryonic polarity by examining the signaling pathways involved. Our preliminary results indicate that Wnt/PCP signaling plays a critical role in this regulation. Furthermore, we will characterize the cell biological mechanism involved in the LRP6 polarity, e.g. differential endocytosis and vesicular trafficking. Finally, we will address what the role of LRP6 polarity plays in regulation of cell fate, notably in neuroectoderm and skin derivatives.