Ttc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polycystic kidney disease

Significance Cilia are tubulin-based cellular appendages, and their dysfunction has been linked to a variety of genetic diseases. Ciliary chondrodysplasia is one such condition that can co-occur with cystic kidney disease and other organ manifestations. We modeled skeletal ciliopathies by mutating two established disease genes in Xenopus tropicalis frogs. Bioinformatic analysis identified ttc30a as a ciliopathy network component, and targeting it replicated skeletal malformations and renal cysts as seen in patients and the amphibian models. A loss of Ttc30a affected cilia by altering posttranslational tubulin modifications. Our findings identify TTC30A/B as a component of ciliary segmentation essential for cartilage differentiation and renal tubulogenesis. These findings may lead to novel therapeutic targets in treating ciliary skeletopathies and cystic kidney disease.