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|Title:||(Don't Call Me Kurly):Investigating the Role of C21Orf59/Kurly, a Novel Scaffold for Cilia Function and Planar Polarity, in PCP and Left-Right Patterning|
|Abstract:||The planar cell polarity (PCP) signaling pathway involves the asymmetric partitioning of cortically localized core proteins in order to produce the collective polarization of cell structures and behaviors along a common axis in the epithelial plane during early development. Notably, PCP plays a key role in coordinating the position and orientation of cilia, which are microtubule-based organelles that play substantial roles in embryogenesis and other physiological processes by generating directional flow and responding to extracellular cues. While the influence of PCP signaling on cilia formation and orientation has been clearly established, evidence supporting the reciprocal regulation of planar cell polarity by cilia has not been solidified. This study addresses the role of a novel protein called C21Orf59/Kurly, previously shown to play a dual function in cilia motility and cilia polarity, for PCP signaling. Primarily, using in vitro protein recruitment assays, we show that Kurly associates with and stabilizes two cytoplasmic core PCP proteins, Dishevelled and Prickle in discrete punctate aggregates that may represent higher-order signaling clusters. We also report preliminary characterizations of laterality defects in c21orf59/kurly mutant embryos generated by CRISPR/Cas9-mediated knockout, which indicate that kurly may play a conserved role in left-right patterning specification as shown in zebrafish systems. These findings contribute valuable insight on a poorly understood mechanistic connection between cilia and PCP during early development and may classify a new molecular target for treatment of cilia-related disease.|
|Type of Material:||Princeton University Senior Theses|
|Appears in Collections:||Molecular Biology, 1954-2020|
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