FIGURE 2.

Cilia-dependent cyst activation (CDCA) model for cystogenesis in ADPKD (adapted from Ma, 2021). (A) The CDCA in the wild-type cell is suppressed by polycystins and is activated through an unknown mechanism, possibly ligand binding to polycystins or flow bending the cilium. (B) In Pkd1 cko, CDCA is derepressed and constitutively activated leading to severe cystogenesis. (C) If Pkd1 and cilia are co-ablated, the CDCA cannot be upregulated. The cystogenic signal is thus diminished compared with single Pkd1 cko, resulting in reduced cystogenesis. In this model, the CDCA signal must retain a partial “leaky” function in the cytoplasm to explain how Pkd1-cilia double mutants display significant cystic changes. (D) In cilia single mutants, there is persistent mild cystogenesis. Here the CDCA must have a leaky function despite the presence of intact polycystins and lack of cilia (“?”). Created in BioRender.