The FOXJ1 target <i>Cfap206</i> is required for sperm motility, mucociliary clearance of the airways and brain development

Abstract

Cilia are complex cellular protrusions consisting of hundreds of proteins. Defects in ciliary structure and function, many of which have not been characterised molecularly, cause ciliopathies: a heterogeneous group of human syndromes. Here, we report on the FOXJ1 target gene <i>Cfap206</i>, orthologues of which so far have only been studied in <i>Chlamydomonas</i> and <i>Tetrahymena</i> In mouse and <i>Xenopus</i>, <i>Cfap206</i> was co-expressed with and dependent on <i>Foxj1</i> CFAP206 protein localised to the basal body and to the axoneme of motile cilia. In <i>Xenopus</i> crispant larvae, the ciliary beat frequency of skin multiciliated cells was enhanced and bead transport across the epidermal mucociliary epithelium was reduced. Likewise, <i>Cfap206</i> knockout mice revealed ciliary phenotypes. Electron tomography of immotile knockout mouse sperm flagella indicated a role in radial spoke formation reminiscent of FAP206 function in <i>Tetrahymena</i> Male infertility, hydrocephalus and impaired mucociliary clearance of the airways in the absence of laterality defects in <i>Cfap206</i> mutant mice suggests that <i>Cfap206</i> may represent a candidate for the subgroup of human primary ciliary dyskinesias caused by radial spoke defects.