Investigating a role for NXN and its interaction with ciliary protein IFT88 in planar cell polarity signaling

The human brain is considered the most complex organ. The early stages of brain development may perhaps be the most crucial time in the brain's formation as neural tube defects occur very early in pregnancy if the neural tube does not close completely. I am interested in the early events that shape the central nervous system, namely: the cell behaviors that shape the neural tube, the precursor of the brain and spinal cord. A signaling pathway called planar cell polarity (PCP) mediates proper cellular behaviors in many tissues, including the developing neural tube. There is an ongoing controversy as to whether cilia mediate PCP signaling during neural tube formation and other developmental processes. Evidence that ciliary proteins are required for neural tube formation stems from the observation that disruption of multiple genes implicated in ciliogenesis results in delayed or blocked neural tube formation. Nevertheless, whether impaired ciliogenesis prevents proper PCP signaling remains unknown. Using a bioinformatics approach, the Kann laboratory recently identified the novel PCP pathway component Nucleoredoxin (Nxn) as a putative bindig partner of the ciliary protein IFT88. Nxn therefore provides a molecular entry point with which to explore the interaction between cilia and PCP signaling. My thesis work centers on validating Nxn as an IFT88 binding partner and testing the predictions that depletion of Nxn should cause similar neural tube defects as those observed in PCP mutants and Nxn should localize to cilia where IFT88 is also enriched. This research lays the framework for future studies on mechanisms of cilia-PCP interactions.