My lab uses zebrafish, a vertebrate system amenable to both genetic and embryonic analyses, to study kidney development and diseases. Currently, we are focusing on polycystic kidney disease (PKD). Understanding PKD is of profound medical importance. Striking one in 1000 live births, autosomal dominant form of PKD (ADPKD) is among the most common monogenetic disorders in humans. PKD1 and PKD2, two genes cloned for ADPKD, encode two membrane proteins polycystin-1 (Pc1) and polycystin-2 (Pc2). Pc1 is a large novel protein, while Pc2 belongs to the TRP channel superfamily, members of which frequently function as mechano-sensory channels. How the functions of Pc1 and Pc2 are regulated, their downstream signaling events, as well as the molecular pathogenesis of PKD remains to be elucidated. In a large-scale insertional mutagenesis screen in zebrafish, I identified 12 genes that can cause kidney cyst when mutated. Two of the genes, vHNF1 and PKD2, are known human PKD genes, indicating that zebrafish cystic kidney mutants are highly relevant to human PKD. Interestingly, three of the mutated genes encode components of IFT (intraflagellar transport) particles, which are required for the formation and maintenance of flagellum and cilium. We are now using this group of cystic kidney mutants as entry points to address multiple questions. First, how is the cilium built during development? Second, how is signal sensed by cilia? Third, how does signal from cilia eventually regulate tube size? Our goal is to tease out the signaling network coupling ciliary signal to size control mechanisms of the renal tube.