Mutations in genes encoding cilia proteins cause human ciliopathies, diverse 
disorders affecting many tissues. Individual genes can be linked to ciliopathies 
with dramatically different phenotypes, suggesting that genetic modifiers may 
participate in their pathogenesis. The ciliary transition zone contains two 
protein complexes affected in the ciliopathies Meckel syndrome (MKS) and 
nephronophthisis (NPHP). The BBSome is a third protein complex, affected in the 
ciliopathy Bardet-Biedl syndrome (BBS). We tested whether mutations in MKS, NPHP 
and BBS complex genes modify the phenotypic consequences of one another in both 
C. elegans and mice. To this end, we identified TCTN-1, the C. elegans ortholog 
of vertebrate MKS complex components called Tectonics, as an evolutionarily 
conserved transition zone protein. Neither disruption of TCTN-1 alone or 
together with MKS complex components abrogated ciliary structure in C. elegans. 
In contrast, disruption of TCTN-1 together with either of two NPHP complex 
components, NPHP-1 or NPHP-4, compromised ciliary structure. Similarly, 
disruption of an NPHP complex component and the BBS complex component BBS-5 
individually did not compromise ciliary structure, but together did. As in 
nematodes, disrupting two components of the mouse MKS complex did not cause 
additive phenotypes compared to single mutants. However, disrupting both Tctn1 
and either Nphp1 or Nphp4 exacerbated defects in ciliogenesis and 
cilia-associated developmental signaling, as did disrupting both Tctn1 and the 
BBSome component Bbs1. Thus, we demonstrate that ciliary complexes act in 
parallel to support ciliary function and suggest that human ciliopathy 
phenotypes are altered by genetic interactions between different ciliary 
biochemical complexes.