Zhang, Q., Liu, Q., Austin, C., Drummond, I., and Pierce, E.A. (2012) Knockdown of ttc26 disrupts ciliogenesis of the photoreceptor cells and the pronephros in zebrafish. Molecular biology of the cell. 23(16):3069-3078.
In our effort to understand genetic disorders of the photoreceptors cells of the retina we have focused on intraflagellar
transport in photoreceptor sensory cilia. From previous mouse proteomic data we identified a cilia protein Ttc26, ortholog
of dyf-13 in C. elegans, as a target. We have localized Ttc26 to the transition zone of photoreceptor and to the transition
zone of cilia in cultured mIMCD3 renal cells. Knockdown of Ttc26 in mIMCD3 cells produced shortened and defective primary cilia, revealed by immunofluorescence and scanning EM respectively.
To study Ttc26 function in sensory cilia in vivo, we utilized a zebrafish vertebrate model system. Morpholino knockdown of
ttc26 in zebrafish embryos caused cilia defects in the pronephric kidney at 27 hpf and distension/dilation of pronephros at 5 dpf.
In the eyes, the outer segments of photoreceptor cells appeared shortened or absent, whereas cellular lamination appeared
normal in retinas at 5 dpf. This suggests that loss of ttc26 function prevents normal ciliogenesis and differentiation in
the photoreceptor cells, and that ttc26 is required for normal development and differentiation in retina and pronephros. Our
studies support the importance of Ttc26 function in ciliogenesis and suggest that screening for TTC26 mutations in human ciliopathies is justified.