Role of FGFRL1 and other FGF signaling proteins in early kidney development
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Cellular and Molecular Life Sciences
REVIEW
Role of FGFRL1 and other FGF signaling proteins in early kidney development Beat Trueb • Ruth Amann • Simon D. Gerber
Received: 14 August 2012 / Revised: 14 September 2012 / Accepted: 25 September 2012 Ó Springer Basel 2012
Abstract The mammalian kidney develops from the ureteric bud and the metanephric mesenchyme. In mice, the ureteric bud invades the metanephric mesenchyme at day E10.5 and begins to branch. The tips of the ureteric bud induce the metanephric mesenchyme to condense and form the cap mesenchyme. Some cells of this cap mesenchyme undergo a mesenchymal-to-epithelial transition and differentiate into renal vesicles, which further develop into nephrons. The developing kidney expresses Fibroblast growth factor (Fgf)1, 7, 8, 9, 10, 12 and 20 and Fgf receptors Fgfr1 and Fgfr2. Fgf7 and Fgf10, mainly secreted by the metanephric mesenchyme, bind to Fgfr2b of the ureteric bud and induce branching. Fgfr1 and Fgfr2c are required for formation of the metanephric mesenchyme, however the two receptors can substitute for one another. Fgf8, secreted by renal vesicles, binds to Fgfr1 and supports survival of cells in the nascent nephrons. Fgf9 and Fgf20, expressed in the metanephric mesenchyme, are necessary to maintain survival of progenitor cells in the cortical region of the kidney. FgfrL1 is a novel member of the Fgfr family that lacks the intracellular tyrosine kinase domain. It is expressed in the ureteric bud and all nephrogenic structures. Targeted deletion of FgfrL1 leads to severe kidney dysgenesis due to the lack of renal vesicles. FgfrL1 is known to interact mainly with Fgf8. It is therefore conceivable that FgfrL1 restricts signaling of Fgf8 to the precise location of the nascent nephrons. It might also promote tight adhesion of cells in the condensed metanephric mesenchyme as required for the mesenchymal-toepithelial transition. B. Trueb (&) R. Amann S. D. Gerber Department of Clinical Research, University of Bern, Murtenstrasse 35, PO Box 43, 3010 Bern, Switzerland e-mail: [email protected]
Keywords Kidney development Metanephric mesenchyme Ureteric bud Fibroblast growth factor (Fgf) Fibroblast growth factor receptor (Fgfr) FgfrL1
Introduction to early kidney development The metanephric (permanent) kidney of higher vertebrates is a complex organ comprising thousands of nephrons that are connected by a branched collecting duct system. The nephrons represent the functional units of the kidney. They filter the blood through a basement membrane and drain the filtrate via tubules and collecting ducts to the bladder. During embryonic development, the metanephric kidney develops from two different tissues, both of which are derived from the intermediate mesoderm, the ureteric bud and the metanephric mesenchyme [1]. In the mouse, development of the permanent kidney is initiated at embryonic day E10.5 when a region of the nephric (Wolffian) duct near the hindlimbs bulges out and gives rise to the ureteric bud. The metanephric mesenchyme sends
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