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• W2104284856 abstract "The planar cell polarity (PCP) pathway, incorporating non-canonical Wnt signalling, controls embryonic convergent (CE) extension, polarized cell division and ciliary orientation. It also limits diameters of differentiating renal tubules, with mutation of certain components of the pathway causing cystic kidneys. Mutations in mouse Vangl genes encoding core PCP proteins cause neural tube defects (NTDs) and Vangl2 mutations also impair branching of embryonic mouse lung airways. Embryonic metanephric kidneys also undergo branching morphogenesis and Vangl2 is known to be expressed in ureteric bud/collecting duct and metanephric mesenchymal/nephron lineages. These observations led us to investigate metanephroi in Vangl2 mutant mice, Loop-tail (Lp). Although ureteric bud formation is normal in Vangl2Lp/Lp embryos, subsequent in vivo and in vitro branching morphogenesis is impaired. Null mutant kidneys are short, consistent with a CE defect. Differentiating glomerular epithelia express several PCP genes (Vangl1/2, Celsr1, Scrib, Mpk1/2 and Fat4) and glomeruli in Vangl2Lp/Lp fetuses are smaller and contain less prominent capillary loops than wild-type littermates. Furthermore, Vangl2Lp/+ kidneys had modest reduction in glomerular numbers postnatally. Vangl2Lp/Lp metanephroi contained occasional dilated tubules but no overt cystic phenotype. These data show for the first time that a PCP gene is required for normal morphogenesis of both the ureteric bud and metanephric mesenchyme-derived structures. It has long been recognized that certain individuals with NTDs are born with malformed kidneys, and recent studies have discovered VANGL mutations in some NTD patients. On the basis of our mutant mouse study, we suggest that PCP pathway mutations should be sought when NTD and renal malformation co-exist." @default.
• W2104284856 created "2016-06-24" @default.
• W2104284856 creator A5018405461 @default.
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• W2104284856 date "2010-09-14" @default.
• W2104284856 modified "2023-10-14" @default.
• W2104284856 title "The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation" @default.
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• W2104284856 doi "https://doi.org/10.1093/hmg/ddq397" @default.
• W2104284856 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2972698" @default.
• W2104284856 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20843830" @default.
• W2104284856 hasPublicationYear "2010" @default.
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