Cilia and flagella are organelles found on diverse cell types in eukaryotes where they function in fluid and cell movement, developmental patterning, and sensory perception. Studies in Chlamydomonas have identified a mechanism for the formation and maintenance of cilia and flagella termed intraflagellar transport (IFT) for which several of the proteins have yet to be identified. Homologs of the known IFT proteins have been identified in organisms as diverse as Chlamydomonas, C. elegans and mouse. Of the complex B IFT proteins identified in C. elegans to date, all are regulated by the transcription factor DAF-19 through a conserved X-box found in the promoter. We used this conserved sequence to search the genome and identified a DAF-19 regulated gene F59C6.7/9 that is located near the che-13
locus. F59C6.7/9is expressed in ciliated sensory neurons in a DAF-19 dependent manner and is required for C. elegans cilia formation. This is evidenced by its disruption in che-13
mutant worms and the transgenic rescue of che-13
cilia defects with expression of F59C6.7/9. In agreement with a role in cilia formation, fluorescent tagged CHE-13 protein concentrates at the base of cilia and moves along the axoneme typical of other IFT proteins. Furthermore, the che-13
mutation differentially affects the localization of two known IFT components supporting its role as an IFT protein. Intriguingly, CHE-13 shares strong homology with the mammalian protein Hippi. When bound to Hip-1, Hippi activates the neuronal apoptotic pathway associated with the Huntington pathology. Expression analysis of the C. elegans homologs of Hip-1 (ZK370.3a/b) and Hippi (che-13
) indicate that they are not expressed in the same cells and are unlikely to form a complex. Furthermore, the tissue and spatial expression profile of mouse Hippi is similar to that of Tg737, a known IFT protein. These data, along with the conservation of the IFT process, suggest that mouse Hippi may function as an IFT protein in addition to its proposed role in neuronal apoptosis in disease conditions.