Evidence that the novel receptor FGFRL1 signals indirectly via FGFR1

Abstract

Fibroblast growth factor (FGF) receptor-like protein 1 (FGFRL1) is a recently discovered member of the FGF receptor (FGFR) family. Similar to the classical FGFRs, it contains three extracellular immunoglobulin-like domains and interacts with FGF ligands. However, in contrast to the classical receptors, it does not contain any intracellular tyrosine kinase domain and consequently cannot signal by transphosphorylation. In mouse kidneys, FgfrL1 is expressed primarily at embryonic stages E14-E15 in regions where nascent nephrons develop. In this study, we used whole-mount in situ hybridization to show the spatial pattern of five different Fgfrs in the developing mouse kidney. We compared the expression pattern of FgfrL1 with that of other Fgfrs. The expression pattern of FgfrL1 closely resembled that of Fgfr1, but clearly differed from that of Fgfr2‑Fgfr4. It is therefore conceivable that FgfrL1 signals indirectly via Fgfr1. The mechanisms by which FgfrL1 affects the activity of Fgfr1 remain to be elucidated.

Figure 1

Analysis of fibroblast growth factor receptor (Fgfr) expression in the mouse kidney. Aliquots (10 μg) of total RNA from mouse kidneys at E15.5 were resolved in parallel on an agarose gel, transferred to a nylon membrane and individually hybridized with radiolabeled probes for Fgfr1, Fgfr2, Fgfr3 and Fgfr4 as indicated. The migration positions of the ribosomal RNAs are indicated in the margin. As a loading control, the ethidium bromide stained 28S ribosomal RNA is shown.

Figure 2

Analysis of FgfrL1 expression during early kidney development. Aliquots of total RNA from mouse kidneys of different developmental stages were resolved on an agarose gel, transferred to a nylon membrane and hybridized with a probe for FgfrL1. The migration positions of the ribosomal RNAs are indicated in the margin. As a loading control, the ethidium bromide stained 28S ribosomal RNA is shown.

Figure 3

Expression patterns of the five fibroblast growth factor receptors (Fgfrs) in mouse kidneys. Kidneys at stage E15.5 were stained by whole-mount in situ hybridization with riboprobes for Fgfr1 (R1), Fgfr2 (R2), Fgfr3 (R3), Fgfr4 (R4), FgfrL1 (RL1) and calbindin 1 (Calb) as indicated. The results demonstrated that the expression pattern of FgfrL1 looked very similar to that of Fgfr1 and the pattern of Fgfr2 similar to that of calbindin. Fgfr3 and Fgfr4 were expressed at very low levels and revealed more complex expression patterns.