Lineage Specification of Parietal Epithelial Cells Requires ... : Journal of the American Society of Nephrology (original) (raw)

Basic Research

Lineage Specification of Parietal Epithelial Cells Requires _β_-Catenin/Wnt Signaling

Grouls, Stephan*,†; Iglesias, Diana Margarita‡; Wentzensen, Nicolas§; Moeller, Marcus Johannes‖; Bouchard, Maxime¶; Kemler, Rolf**; Goodyer, Paul‡; Niggli, Felix††; Gröne, Hermann-Josef‡‡; Kriz, Wilhelm§§; Koesters, Robert‖‖

*Department of Nephrology and

†Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany;

‡Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, McGill University Health Centre Research Institute and McGill University, Montreal, Quebec, Canada;

§Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland;

‖Department of Nephrology and Clinical Immunology, University Hospital of Rheinisch-Westfaelische Technische Hochschule Aachen University, Aachen, Germany;

¶Goodman Cancer Centre, Department of Biochemistry, McGill University, Montreal, Quebec, Canada;

**Department of Molecular Embryology, Max Planck Institute for Immunobiology, Freiburg, Germany;

††Children's Hospital, University of Zurich, Zurich, Switzerland;

‡‡Division of Cellular and Molecular Pathology, Deutsches Krebsforschungszentrum, Heidelberg, Germany;

§§Ruperto-Carola University of Heidelberg, Anatomy and Developmental Biology, Medical Faculty Mannheim, Mannheim, Germany; and

‖‖INSERM Unit 702, University of Paris 6, Hospital Tenon, Paris, France

Correspondence: Mr. Stephan Grouls, University of Heidelberg, Department of Nephrology, Im Neuenheimer Feld 162, 69120 Heidelberg, Baden-Württemberg, Germany. Email: [email protected]

Received December 12, 2010

Accepted August 9, 2011

Abstract

_β_-Catenin/Wnt signaling is essential during early inductive stages of kidney development, but its role during postinductive stages of nephron development and maturation is not well understood. In this study, we used Pax8Cre mice to target _β_-catenin deficiency to renal epithelial cells at the late S-shaped body stage and the developing collecting ducts. The conditional _β_-catenin knockout mice formed abnormal kidneys and had reduced renal function. The kidneys were hypoplastic with a thin cortex; a superficial layer of tubules was missing. A high proportion of glomeruli had small, underdeveloped capillary tufts. In these glomeruli, well differentiated podocytes replaced parietal epithelial cells in Bowman’s capsule; capillaries toward the outer aspect of these podocytes mimicked the formation of glomerular capillaries. Tracing nephrogenesis in embryonic conditional _β_-catenin knockout mice revealed that these “parietal podocytes” derived from precursor cells in the parietal layer of the S-shaped body by direct lineage switch. Taken together, these findings demonstrate that _β_-catenin/Wnt signaling is important during the late stages of nephrogenesis and for the lineage specification of parietal epithelial cells.