title: Nephrons require Rho-kinase for proximal-distal polarity development.
abstract: Epithelial tubules must have the right length and pattern for proper function. In the nephron, planar cell polarity controls elongation along the proximal-distal axis. As the tubule lengthens, specialized segments (proximal, distal etc.) begin to differentiate along it. Other epithelia need Rho-kinase for planar cell polarity but it is not known whether Rho-kinase is involved in this way in the nephron. We show that Rho-kinase is essential for the morphogenesis of nephrons, specifically for correct cell orientation and volume. We use fluorescent reporter-models and progenitor-specific markers to demonstrate that inhibition of Rho-kinase prevents proper proximal-distal axis formation, causes segments to develop abnormally, and progenitor-cell segregation to fail. Our data demonstrate the importance of Rho-kinase in normal nephron tubulogenesis and patterning.
authors.affiliation: 1] Centre for Integrative Physiology, The University of Edinburgh, Hugh Robson Building, EH8 9XB, United Kingdom [2] MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom [3] The Roslin Institute, The University of Edinburgh, Easter Bush, EH25 9RG, United Kingdom.
authors.forename: Nils O
authors.initials: NO
authors.lastname: Lindström
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Davies
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D007684:Kidney Tubules / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009399:Nephrons / Q000196:embryology* / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D054460:rho-Associated Kinases
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