The Role of Cilia in the Development, Survival, and Regeneration of Hair Cells

Mutations impacting cilia genes lead to a class of human diseases known as ciliopathies. This is due to the role of cilia in the development, survival, and regeneration of many cell types. We investigated the extent to which disrupting cilia impacted these processes in hair cells. We found that mutations in two intraflagellar transport (IFT) genes, ift88 and dync2h1, which lead to the loss of kinocilia, the primary cilia of hair cells, caused an increase in hair cell apoptosis in the zebrafish lateral line. These IFT gene mutants show a decreased mitochondrial membrane potential, and blocking the mitochondrial uniporter causes a loss of hair cells in wild-type zebrafish but not in IFT gene mutants. This suggests mitochondria dysfunction may contribute to the apoptosis seen in these mutants. In contrast to its role in hair cell survival, dync2h1 does not appear important for proliferation during hair cell development, but ift88 may be. There is also a reduction in both proliferation and the number of hair cells after regeneration in both IFT gene mutants. These results show that disruption of the cilia through either mutations in anterograde or retrograde IFT genes appear to decrease hair cell survival and regeneration in the lateral line, with ift88 specifically, potentially playing an additional role in hair cell development.