The role of vang-1/Van Gogh in the ciliated neurons of C. elegans

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Cilia are sensory or motile organelles found on the surface of most eukaryotic cells. Recently, planar cell polarity (PCP) signaling, a well-established regulator of cellular polarity along the surface of epithelial cells, has been implicated in cilia formation, orientation, and function. My laboratory uses C. elegans as a model to investigate the role of PCP signaling in neuronal morphology and function. We have recently shown that worm orthologues of the core PCP proteins VANG-1/Van Gogh and PRKL-1/Prickle are expressed in specific subsets of ciliated sensory neurons (CEP neurons) or support cells (CEP sheath cells) in the worm head. In addition, a GFP translational fusion showed a specific accumulation of VANG-1 to the cilia (transition zone) located at the distal tip of CEP dendrites. We hypothesize that VANG-1 in CEP neurons acts through a PCP-like mechanism, that may include PRKL-1 in CEPsh cells, to properly polarize structures at the dendritic tip that are important for cilia formation, maintenance, or sensory function. We therefore propose to identify the role of VANG-1 and other core PCP pathway components like PRKL-1 in ciliated neurons, investigate genetic and cellular pathways that require VANG-1 in the transition zone of cilia, and identify and characterize new components required to specifically localize VANG-1 to cilia or interact directly or indirectly with VANG-1 in the cilia of CEP neurons. Ultimately, this research program should help us better understand the relationship between PCP-like signaling and cilia as well as provide new insight into the role of PCP pathway components in neuronal cells.