Study related to kidney disease uses flies as in vivo test model for follow-up of genes identified in a human cell-based screen

Cina DP, Ketela T, Brown KR, Chandrashekhar M, Mero P, Li C, Onay T, Fu Y, Han Z, Saleem MA, Moffat J, Quaggin SE. Forward genetic screen in human podocytes identifies diphthamide biosynthesis genes as regulators of adhesion. Am J Physiol Renal Physiol. 2019 Sep 30. doi: 10.1152/ajprenal.00195.2019. PubMed PMID: 31566424.

From the abstract: "... To identify novel genes that are important for podocyte function, we designed an in vitro genetic screen based on podocyte adhesion to plates coated with either fibronectin or soluble FLT1/Fc. .. A genome-scale pooled RNA interference screen on immortalized human podocytes identified 77 genes that increased adhesion to fibronectin, 101 genes that increased adhesion to sFLT1/Fc, and 44 genes that increased adhesion to both substrates when knocked down. Multiple shRNAs against each of DPH1, DPH2, DPH3, and DPH4 were top hits ... We then used CRISPR-Cas9 to generate podocyte knockout cells for DPH1, DPH2, or DPH3 which also displayed increased adhesion ... as well as a spreading defect. Last, we showed that Drosophila nephrocyte-specific knock-down of Dph1, Dph2, and Dph4 results in altered nephrocyte function. ... Given the central role of podocyte adhesion as a marker of podocyte health, these data are a rich source of candidate regulators of glomerular disease."