Novel roles for the radial spoke head protein 9 in neural and neurosensory cilia

• Published in: Scientific reports Vol. 6; no. 1; p. 34437
• Main Authors: Sedykh, Irina, TeSlaa, Jessica J., Tatarsky, Rose L., Keller, Abigail N., Toops, Kimberly A., Lakkaraju, Aparna, Nyholm, Molly K., Wolman, Marc A., Grinblat, Yevgenya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.09.2016; Nature Publishing Group
• Subjects: 14/19; 14/28; 38/70; 631/136/2060/368/2430; 631/80/304; 64/116; Acoustic startle response; Axonemes; Cell surface; CRISPR; Dyskinesia; Fluid flow; Hearing loss; Humanities and Social Sciences; Inner ear; Lateral line; Motility; multidisciplinary; Mutagenesis; Mutation; Neuromasts; Olfactory cilia; Organelles; Primary ciliary dyskinesia; Proteins; Roles; Science; Science (multidisciplinary); Science education; Spinal cord; Startle response; Zebrafish
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep34437

Cilia are cell surface organelles with key roles in a range of cellular processes, including generation of fluid flow by motile cilia. The axonemes of motile cilia and immotile kinocilia contain 9 peripheral microtubule doublets, a central microtubule pair, and 9 connecting radial spokes. Aberrant radial spoke components RSPH1, 3, 4a and 9 have been linked with primary ciliary dyskinesia (PCD), a disorder characterized by ciliary dysmotility; yet, radial spoke functions remain unclear. Here we show that zebrafish Rsph9 is expressed in cells bearing motile cilia and kinocilia, and localizes to both 9 + 2 and 9 + 0 ciliary axonemes. Using CRISPR mutagenesis, we show that rsph 9 is required for motility of presumptive 9 + 2 olfactory cilia and, unexpectedly, 9 + 0 neural cilia. rsph 9 is also required for the structural integrity of 9 + 2 and 9 + 0 ciliary axonemes. rsph 9 mutant larvae exhibit reduced initiation of the acoustic startle response consistent with hearing impairment, suggesting a novel role for Rsph9 in the kinocilia of the inner ear and/or lateral line neuromasts. These data identify novel roles for Rsph9 in 9 + 0 motile cilia and in sensory kinocilia, and establish a useful zebrafish PCD model.