Oral-facial-digital syndrome type1 (OFD1) is an inherited disorder caused by expression of mutant OFD1 protein and results in abnormalities in facial and limb development and polycystic kidney disease that resembles Autosomal Dominant Polycystic Kidney Disease (ADPKD). The similarities in renal disease pathogenesis in patients with OFD1 and ADPKD suggest that the proteins implicated in these diseases, OFD1 and the polycystins, respectively, function on a common pathway in the affected cell types. This calls for an investigation to uncover the mechanism by which OFD1 contributes to polycystic kidney disease pathogenesis, which remains unknown. This thesis details for the first time the assembly of a ciliary signaling microdomain containing OFD1, the polycystins, the epidermal growth factor receptor (EGFR), and the domain organizing flotillin proteins in renal epithelia and cells of the oral cavity. Also, the studies presented here provide a mechanism by which OFD1, a soluble protein, is trafficked to primary cilia via its interaction with polycystin-1 (PC1), a ciliary membrane protein. The presented data demonstrate the requirement of coiled coil domains found in both OFD1 and PC1 for OFD1 interaction with PC1 and proper localization of OFD1 to primary cilia. The composite work provides the foundation for identifying potential molecular targets for therapeutic interventions for the millions of individuals suffering from polycystic kidney disease worldwide.
cystic kidney, kidney epithelia, ciliopathy, inherited kidney disease, dental and craniofacial diseases, primary cilia, microdomain
Level of Degree
Biomedical Sciences Graduate Program
First Committee Member (Chair)
Second Committee Member
Third Committee Member
Jerman, Stephanie. "The Role of OFD1 in the Pathogenesis of Polycystic Kidney Disease." (2015). https://digitalrepository.unm.edu/biom_etds/154