Nephrons require Rho-kinase for proximal-distal polarity development

• Published in: Scientific reports Vol. 3; no. 1; p. 2692
• Main Authors: Lindström, Nils O., Hohenstein, Peter, Davies, Jamie A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.09.2013; Nature Publishing Group
• Subjects: 631/136/1660/2176; 631/136/756/1456; 631/80/128/1675; 631/80/85/2361; Animals; Cell Differentiation; Cell Polarity - drug effects; Cell Polarity - physiology; Elongation; Humanities and Social Sciences; Kidney Tubules - embryology; Kidney Tubules - metabolism; Kidneys; Kinases; Mice; Mice, Transgenic; Morphogenesis; Morphology; multidisciplinary; Nephrons; Nephrons - embryology; Nephrons - metabolism; Polarity; Progenitor cells; Protein Kinase Inhibitors - pharmacology; Rho-associated kinase; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; Science; Stem Cells - cytology; Stem Cells - metabolism; Tubules
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep02692

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.