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

Abstract

ABSTRACTMutations 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,ift88anddync2h1,which lead to the loss of kinocilia, caused increased hair cell apoptosis in the zebrafish lateral line. IFT gene mutants also have a decreased mitochondrial membrane potential, and blocking the mitochondrial uniporter causes a loss of hair cells in wild-type zebrafish but not mutants, suggesting mitochondria dysfunction may contribute to the apoptosis seen in these mutants. These mutants also showed decreased proliferation during hair cell regeneration, but did not show consistent changes in support cell number or proliferation during hair cell development. These results show that disruption of the cilia through either mutations in anterograde or retrograde IFT genes appear to impact hair cell survival but not necessarily development in the lateral line.