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The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation

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 cys...

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Autores principales: Yates, Laura L., Papakrivopoulou, Jenny, Long, David A., Goggolidou, Paraskevi, Connolly, John O., Woolf, Adrian S., Dean, Charlotte H.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2972698/
https://www.ncbi.nlm.nih.gov/pubmed/20843830
http://dx.doi.org/10.1093/hmg/ddq397
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author Yates, Laura L.
Papakrivopoulou, Jenny
Long, David A.
Goggolidou, Paraskevi
Connolly, John O.
Woolf, Adrian S.
Dean, Charlotte H.
author_facet Yates, Laura L.
Papakrivopoulou, Jenny
Long, David A.
Goggolidou, Paraskevi
Connolly, John O.
Woolf, Adrian S.
Dean, Charlotte H.
author_sort Yates, Laura L.
collection PubMed
description 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 Vangl2(Lp/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 Vangl2(Lp/Lp) fetuses are smaller and contain less prominent capillary loops than wild-type littermates. Furthermore, Vangl2(Lp/+) kidneys had modest reduction in glomerular numbers postnatally. Vangl2(Lp/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.
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spelling pubmed-29726982010-11-05 The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation Yates, Laura L. Papakrivopoulou, Jenny Long, David A. Goggolidou, Paraskevi Connolly, John O. Woolf, Adrian S. Dean, Charlotte H. Hum Mol Genet Articles 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 Vangl2(Lp/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 Vangl2(Lp/Lp) fetuses are smaller and contain less prominent capillary loops than wild-type littermates. Furthermore, Vangl2(Lp/+) kidneys had modest reduction in glomerular numbers postnatally. Vangl2(Lp/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. Oxford University Press 2010-12-01 2010-09-14 /pmc/articles/PMC2972698/ /pubmed/20843830 http://dx.doi.org/10.1093/hmg/ddq397 Text en © The Author 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Yates, Laura L.
Papakrivopoulou, Jenny
Long, David A.
Goggolidou, Paraskevi
Connolly, John O.
Woolf, Adrian S.
Dean, Charlotte H.
The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation
title The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation
title_full The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation
title_fullStr The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation
title_full_unstemmed The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation
title_short The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation
title_sort planar cell polarity gene vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2972698/
https://www.ncbi.nlm.nih.gov/pubmed/20843830
http://dx.doi.org/10.1093/hmg/ddq397
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