All ETDs from UAB

Advisory Committee Chair

Bradley K Yoder

Advisory Committee Members

Jim Collawn

Alecia Gross

John Parant

Rosa Serra

Jianbo Wang

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


Primary cilia are highly conserved microtubule-based appendages that are present on the surface of nearly every mammalian cell type, and function as signaling hubs for the cell. Their function depends on their ability to assemble, traffic signaling components into and out of the cilium, and disassemble. These events require precise coordination of ciliary machinery and regulation of ciliary infrastructure including, but not limited to, the ciliary basal bodies, transition zone (TZ), and BBSome. The basal bodies reside at the base of the cilium and serve as the foundation for ciliary axoneme construction. Distal to the basal bodies is the TZ, which serves a gatekeeper-like role in regulating entry and exit to the ciliary compartment. The BBSome is an octomeric coat-like protein complex that mediates bidirectional transport of transmembrane proteins across the TZ. Nphp4 and Bbs5 are components of the TZ and BBSome, respectively, and are a focus of the first part of this dissertation. This work includes an in-depth evaluation of one component of the BBSome, BBS5, using a new mutant mouse model. Using this new model, I investigate the evolutionary conserva-tion of genetic interactions between Nphp4 and Bbs5 first identified in C. elegans by assessing the consequence of disrupting these interactions in the zebrafish and mouse models. Interestingly, studies in zebrafish indicate that interactions are not conserved; however, studies in mice indicate that genetic interactions are important and loss of both NPHP4 and BBS5 results in pre-weaning lethality and neurological abnormalities, which are not present in either individual mutant. I also assess the function of ATXN10, which was predicted to have ciliary roles based on informatic analysis. I show that, while ATXN10 is dispensable for ciliogenesis, it is enriched around the base of the cilium. Most significantly, I show that loss of ATXN10 is essential for viability during both embryonic development and post-nataly. Loss of ATXN10 in adult mice causes the pancreatic epithelium to transition to a more progenitor-like state and a renal Epithelial to Mesenchymal Transition. Future work will be focused on assessing whether this is related to ATXN10 function at the base of the cilium.



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