Fig. 8

Ciliopathies most commonly arise from the dysfunction of well-characterised functional modules (ciliopathy modules), namely the basal body, the transition zone (TZ) ciliary gate, intraflagellar transport (IFT) or IFT-associated BBS cargo-trafficking system, a variety of signalling proteins, and a motility apparatus specific to motile cilia. Distinct from these macromolecular complexes are proteins within and near the IJ including CFAP20, PACRG and potentially CFAP52, which may represent a previously unknown ciliopathy module that influences ciliary beat patterns (motility) likely by acting via radial spokes (RS) and the Nexin-Dynein Regulatory Complex (N-DRC). Our study confirms a role for zebrafish CFAP20 in metazoan motile cilia, implicating it as a strong candidate for the motile ciliopathy, primary ciliary dyskinesia (PCD). In C. elegans, CFAP20 and PACRG independently regulate the signalling functions of different classes of non-motile cilia. Lastly, mutations in human CFAP20 result in retinal dystrophy, a ciliary photoreceptor degeneration phenotype that is phenocopied in zebrafish CFAP20 mutant animals. In these non-motile cilia, the IJH may influence, structurally and/or functionally, currently unknown signalling proteins, and represents a previously unknown disease locus for photoreceptor degeneration. IDA Inner Dynein Arm, ODA Outer Dynein Arm, BBS Bardet-Biedl syndrome. Shapes and symbols in this schematic are also represented in the complementary Fig. 1.