Dynamics of vertebrate planar cell polarity proteins

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 DESCRIPTION (provided by applicant): The Planar Cell Polarity (PCP) signaling system is an evolutionarily conserved genetic module that controls polarized cell behavior in animals and is broadly essential for vertebrate development. Among the many behaviors controlled by PCP signaling is the oriented beating of motile cilia, which is central to generating the fluid flow tht is crucial for homeostasis and function in many organ systems, including the airway. Despite the fact that mutation of PCP genes in humans is associated with diverse structural birth defects, studies of PCP protein dynamics have been largely limited to Drosophila, which unlike mammals is highly amenable to live imaging. The immediate goal of this proposal is to develop and exploit novel tools for exploring the dynamics of PCP proteins via live imaging in a vertebrate ciliated epithelium. Understanding the mechanisms of PCP function is an important challenge in developmental biology, and this proposal will generate new, easily adopted tools for the community. Moreover, the proposed experiments will substantially advance our understanding of vertebrate-specific mechanisms of PCP signaling, providing insights into human structural birth defects such as neural tube defects and congenital limb anomalies.