title: Independent roles of Fgfr2 and Frs2alpha in ureteric epithelium.
abstract: Mice with conditional deletion of fibroblast growth factor receptor 2 (Fgfr2) in the ureteric bud using a Hoxb7cre line (Fgfr2(UB-/-)) develop severe ureteric branching defects; however, ureteric deletion of fibroblast growth factor receptor substrate 2α (Frs2α), a key docking protein that transmits fibroblast growth factor receptor intracellular signaling (Frs2α(UB-/-)) leads to mild ureteric defects. Mice with point mutations in the Frs2α binding site of Fgfr2 (Fgfr2(LR/LR)) have normal kidneys. The aim of this study was to determine the relationship between Fgfr2 and Frs2α in the ureteric lineage. Mice with ureteric deletion of both Fgfr2 and Frs2α (Fgfr2/Frs2α(UB-/)) were compared with Frs2α(UB-/-) and Fgfr2(UB-/-) mice. To avoid potential rescue of Fgfr1 forming heterodimers with Fgfr2(LR) alleles to recruit Frs2α, compound mutant mice were generated with ureteric deletion of Fgfr1 and with Fgfr2(LR/LR) point mutations (Fgfr1(UB-/-)Fgfr2(LR/LR)). At E13.5, three-dimensional reconstructions and histological assessment showed that, whereas Fgfr2(UB-/-) kidneys had more severe ureteric branching defects than Frs2α(UB-/-), Fgfr2(UB-/-) kidneys were indistinguishable from Fgfr2/Frs2α(UB-/-). At later stages, however, Fgfr2/Frs2α(UB-/-) kidneys were more severely affected than either Fgfr2(UB-/-) or Frs2α(UB-/-) kidneys. Taken together, although Fgfr2 and Frs2α have crucial roles in the ureteric lineage, they appear to act separately and additively.
authors.affiliation: Rangos Research Center, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15201, USA.
authors.forename: Sunder
authors.initials: S
authors.lastname: Sims-Lucas
authors.forename: Brian
authors.initials: B
authors.lastname: Cusack
authors.forename: Veraragavan P
authors.initials: VP
authors.lastname: Eswarakumar
authors.forename: Jue
authors.initials: J
authors.lastname: Zhang
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: Carlton M
authors.initials: CM
authors.lastname: Bates
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004848:Epithelium / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D014513:Ureter / Q000378:metabolism*
chemical_list: C488187:FRS2alpha protein, mouse; D008565:Membrane Proteins; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2