Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common heritable diseases in the world, characterized by the development of large fluid filled cyst. Treatments for this disease are limited due to a lack of understanding of disease pathogenesis. Ca2+/calmodulin dependent protein kinase II (CaMK-II) is necessary for kidney morphogenesis in zebrafish as well as being a downstream effector of pkd2, one of the genes most commonly mutated in ADPKD patients. The roles of CaMK-II during zebrafish kidney development include regulation of kidney cell migration as well as cloacal cilia stability. The influence of CaMK-II on these pathways is partially dependent on its regulation of HDAC4 localization. Inhibition of CaMK-II caused the translocation of HDAC4 from the cytosol to the nucleus, leading to the model that CaMK-II activation via PKD2 retains HDAC4 in the cytosol allowing for transcription of its target genes. Further studies attempted with a zebrafish camk2g1 mutant proved inconclusive as mutants displayed none of the phenotypic defects seen in morphant embryos. Analysis of CaMK-II gene expression in camk2g1 mutants identified the capability of genetic compensation between CaMK-II family members. In camk2g1 mutants, the paralog gene camk2g2 is upregulated over 3 fold, compensating for the loss of its paralog gene. In conclusion, this study has furthered the understanding of the roles of CaMK-II during kidney development and demonstrated the ability of CaMK-II family members to compensate for one other. In addition, this study also further validates the uses of knockdown methods in developmental studies
