Drosophila model of polycystic kidney disease leads to mechanistic insights

Gamberi C, Hipfner DR, Trudel M, Lubell WD. Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila. PLoS Genet. 2017 Apr 13;13(4):e1006694. PMID: 28406902; PMCID: PMC5390980.

The abstract: "Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called "Malpighian" tubules) and reduced renal function. The BicC protein was shown to bind to Drosophila (d-) myc mRNA in tubules. Elevation of d-Myc protein levels was a cause of tubular degeneration in BicC mutants. Activation of the Target of Rapamycin (TOR) kinase pathway, another common feature of PKD, was found in BicC mutant flies. Rapamycin administration substantially reduced the cystic phenotype in flies. We present new mechanistic insight on BicC function and propose that Drosophila may serve as a genetically tractable model for dissecting the evolutionarily-conserved molecular mechanisms of renal cystogenesis."

Flies & kidney disease

Tutor AS, Prieto-Sánchez S, Ruiz-Gómez M. Src64B phosphorylates Dumbfounded and regulates slit diaphragm dynamics: Drosophila as a model to study nephropathies. Development. 2013 Dec 11. PMID: 24335255.

Planar Cell Polarity and Kidney Development. Recent review.

This review provides a background on the role of planar cell polarity (PCP), a topic well studied in Drosophila, in the mammalian kidney. The material reviewed is primarily relevant to kidney development but also has relevance to polycystic kidney disease, etc.

Carroll TJ, Yu J. The kidney and planar cell polarity. Curr Top Dev Biol. 2012;101:185-212. doi: 10.1016/B978-0-12-394592-1.00011-9. PubMed PMID: 23140630.