Basic ResearchRecombination Signal Binding Protein for Ig-κJ Region Regulates Juxtaglomerular Cell Phenotype by Activating the Myo-Endocrine Program and Suppressing Ectopic Gene ExpressionCastellanos-Rivera, Ruth M.*,†; Pentz, Ellen S.*; Lin, Eugene*,†; Gross, Kenneth W.‡; Medrano, Silvia*; Yu, Jing§; Sequeira-Lopez, Maria Luisa S.*; Gomez, R. Ariel*,† Author Information *Department of Pediatrics, School of Medicine, †Department of Biology, Graduate School of Arts and Sciences, and §Department of Cell Biology, University of Virginia, Charlottesville, Virginia; and ‡Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York Correspondence: Dr. R. Ariel Gomez, University of Virginia, School of Medicine, 409 Lane Road, MR4 Building 2001, Charlottesville, VA 22908. Email: [email protected] Received October 4, 2013 Accepted April 4, 2014 Journal of the American Society of Nephrology 26(1):p 67-80, January 2015. | DOI: 10.1681/ASN.2013101045 Buy Metrics Abstract Recombination signal binding protein for Ig-κJ region (RBP-J), the major downstream effector of Notch signaling, is necessary to maintain the number of renin-positive juxtaglomerular cells and the plasticity of arteriolar smooth muscle cells to re-express renin when homeostasis is threatened. We hypothesized that RBP-J controls a repertoire of genes that defines the phenotype of the renin cell. Mice bearing a bacterial artificial chromosome reporter with a mutated RBP-J binding site in the renin promoter had markedly reduced reporter expression at the basal state and in response to a homeostatic challenge. Mice with conditional deletion of RBP-J in renin cells had decreased expression of endocrine (renin and Akr1b7) and smooth muscle (Acta2, Myh11, Cnn1, and Smtn) genes and regulators of smooth muscle expression (miR-145, SRF, Nfatc4, and Crip1). To determine whether RBP-J deletion decreased the endowment of renin cells, we traced the fate of these cells in RBP-J conditional deletion mice. Notably, the lineage staining patterns in mutant and control kidneys were identical, although mutant kidneys had fewer or no renin-expressing cells in the juxtaglomerular apparatus. Microarray analysis of mutant arterioles revealed upregulation of genes usually expressed in hematopoietic cells. Thus, these results suggest that RBP-J maintains the identity of the renin cell by not only activating genes characteristic of the myo-endocrine phenotype but also, preventing ectopic gene expression and adoption of an aberrant phenotype, which could have severe consequences for the control of homeostasis. Copyright © 2015 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.