Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development.
Fibroblast growth factor receptors (Fgfrs) have critical roles in kidney development. FgfrIIIb is thought to act in epithelium, while FgfrIIIc functions in mesenchyme. We aimed to determine roles of Fgfr2IIIc in kidney development. Mice with deletion of Fgfr2IIIc (Fgfr2IIIc-/-) had normal kidneys. Combination of Fgfr2IIIc-/- with conditional deletion of Fgfr1 in metanephric mesenchyme (MM) (Fgfr1(Mes-/-)Fgfr2IIIc-/-) had small but identifiable MM at embryonic day (E) 10.5, expressing mesenchymal markers including Eya1, Six2, Pax2, and Gdnf (unlike Fgfr1/2(Mes-/-) mice that have no obvious MM). E11.5 Fgfr1(Mes-/-)Fgfr2IIIc-/- mice had rudimentary MM expressing only Eya1. Control, Fgfr2IIIc-/-, and Fgfr1(Mes-/-)Fgfr2IIIc-/- kidney mesenchymal tissues also express Fgfr2IIIb. In ureteric lineages, E10.5 Fgfr1(Mes-/-)Fgfr2IIIc-/- embryos had ureteric outgrowth (sometimes multiple buds); however, by E11.5 Gdnf absence lead to no ureteric elongation or branching (similar to Fgfr1/2(Mes-/-) mice). Beyond E12.5, Fgfr1(Mes-/-)Fgfr2IIIc-/- mice had no renal tissue. In conclusion, Fgfr2IIIc and Fgfr1 in kidney mesenchyme (together) are critical for normal early renal development.
Rangos Research Center, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
Sunder
S
Sims-Lucas
Brian
B
Cusack
Jeffrey
J
Baust
Veraragavan P
VP
Eswarakumar
Hagiwara
H
Masatoshi
Akihide
A
Takeuchi
Carlton M
CM
Bates
D000818:Animals; D002478:Cells, Cultured; D003198:Computer Simulation; D004622:Embryo, Mammalian; D004627:Embryonic Induction / Q000235:genetics*; D007668:Kidney / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009399:Nephrons / Q000196:embryology / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014513:Ureter / Q000196:embryology / Q000378:metabolism
D020033:Protein Isoforms; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2