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Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat
B Cancilla1, M D Ford-Perriss, J F Bertram
1Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia.
Unlabelled:
Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney.
Background:
The permanent kidney, or metanephros, develops through a complex series of reciprocal inductive events and involves branching morphogenesis, tubulogenesis, angiogenesis, and tissue remodeling. Fibroblast growth factors (FGFs) are a family of growth and differentiation factors that have been implicated in metanephric development. FGFs exert their actions through tyrosine kinase receptors, FGFRs, which are encoded by four FGFR genes (FGFR1 through FGFR4).
Methods:
Reverse transcriptase-polymerase chain reaction was used to detect the expression of FGFs and FGFRs in rat metanephroi from embryonic day (E) 14 to E21. Nonradioactive in situ hybridization was used to localize FGF1 mRNA in E20 rat metanephroi, and immunohistochemistry was used to localize FGFRs in E15 and E20 rat metanephroi.
Results:
We detected the expression of mRNAs for FGF1 through FGF5, FGF7 through FGF10, and FGFR1 through FGFR4 (IIIb and IIIc splice variants) in rat metanephroi from E14 to E21. By in situ hybridization, FGF1 mRNA was detected in the nephrogenic zone, ureteric epithelium, and developing nephron elements. FGFR proteins were localized in a distinct pattern that altered with maturation. FGFR1 was widely distributed in developing metanephric epithelia and mesenchyme, but not in developing interstitium. FGFR2 was also widely distributed in nephron epithelia, particularly in proximal convoluted tubules, but was not detected in metanephric mesenchyme, mesenchymal condensates, or developing interstitium. FGFR3 was localized to mesenchymal condensates, nephron elements, and medullary interstitium but not proximal convoluted tubules. FGFR4 was localized mostly to maturing nephron structures and was not detected in nephrogenic mesenchyme, mesenchymal condensates, or developing interstitium.
Conclusions:
These results indicate that FGFs and FGFRs are expressed in the developing rat metanephros from at least E14 and that they likely play important roles in metanephric development and maturation.
Insights
Fibroblast growth factors (FGFs) and their receptors (FGFRs) are expressed in developing rat kidneys. These molecules play crucial roles in kidney development and maturation from embryonic day 14 onwards.
Area of Science:
- Developmental Biology
- Molecular Biology
- Nephrology
Background:
- The permanent kidney (metanephros) develops via complex inductive events, including branching morphogenesis and tubulogenesis.
- Fibroblast growth factors (FGFs) are key regulators implicated in metanephric development.
- FGFs signal through tyrosine kinase receptors (FGFRs), encoded by four genes (FGFR1-4).
Purpose of the Study:
- To investigate the expression and localization of FGFs and FGFRs during rat kidney development.
- To elucidate the potential roles of FGF-FGFR signaling in metanephric morphogenesis and maturation.
Main Methods:
- Reverse transcriptase-polymerase chain reaction (RT-PCR) to detect FGF and FGFR mRNA expression in rat metanephroi (embryonic day 14-21).
- Nonradioactive in situ hybridization to localize FGF1 mRNA.
- Immunohistochemistry to localize FGFR protein distribution.
Main Results:
- mRNAs for FGF1-5, FGF7-10, and FGFR1-4 (including splice variants) were detected throughout rat metanephric development (E14-21).
- FGF1 mRNA localized to the nephrogenic zone and developing nephron structures.
- FGFR proteins exhibited distinct, stage-specific localization patterns within the developing kidney, with differential distribution in epithelia, mesenchyme, and interstitial compartments.
Conclusions:
- FGFs and FGFRs are expressed in the developing rat metanephros starting from at least embryonic day 14.
- The distinct expression patterns suggest significant roles for FGF-FGFR signaling in regulating key processes of kidney development and maturation.
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