Comparison of the Gene Expression Profiles from Normal and Fgfrl1 Deficient Mouse Kidneys Reveals Downstream Targets of Fgfrl1 Signaling

Simon D Gerber,Ruth Amann,Beat Trueb,Stefan Wyder

doi:10.1371/journal.pone.0033457

Abstract

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron.

Highlights

The mammalian kidney is a complex organ comprising thousands of nephrons that are connected by a branched collecting duct system [1]
In the present study we used the DNA microarray profiling technique to identify genes that act downstream of Fgfrl1 signaling in the regulatory hierarchy of genes required for early nephron development
Fgfrl1 is expressed throughout metanephric kidney development

Summary

Introduction

The mammalian kidney is a complex organ comprising thousands of nephrons that are connected by a branched collecting duct system [1]. Nephron development is initiated at E10.5 when a caudal portion of the Wolffian duct near the hindlimbs bulges out and forms the ureteric bud. Signals from the metanephric mesenchyme induce the ureteric bud to branch in a stereotypical fashion to form the highly branched collecting duct system. The ureteric bud in turn releases signals that induce the metanephric mesenchyme to condense around the tips of the ureteric bud and to form the cap mesenchyme. Some cells of the cap mesenchyme undergo a mesenchymal-to-epithelial transition and develop into renal vesicles. These vesicles elongate, form s-shaped bodies and mature into nephrons

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Conclusion