Independent roles of Fgfr2 and Frs2alpha in ureteric epithelium. Academic Article uri icon

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 2 (Frs2), a key docking protein that transmits fibroblast growth factor receptor intracellular signaling (Frs2(UB-/-)) leads to mild ureteric defects. Mice with point mutations in the Frs2 binding site of Fgfr2 (Fgfr2(LR/LR)) have normal kidneys. The aim of this study was to determine the relationship between Fgfr2 and Frs2 in the ureteric lineage. Mice with ureteric deletion of both Fgfr2 and Frs2 (Fgfr2/Frs2(UB-/)) were compared with Frs2(UB-/-) and Fgfr2(UB-/-) mice. To avoid potential rescue of Fgfr1 forming heterodimers with Fgfr2(LR) alleles to recruit Frs2, 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 Frs2(UB-/-), Fgfr2(UB-/-) kidneys were indistinguishable from Fgfr2/Frs2(UB-/-). At later stages, however, Fgfr2/Frs2(UB-/-) kidneys were more severely affected than either Fgfr2(UB-/-) or Frs2(UB-/-) kidneys. Taken together, although Fgfr2 and Frs2 have crucial roles in the ureteric lineage, they appear to act separately and additively.

published proceedings

  • Development

author list (cited authors)

  • Sims-Lucas, S., Cusack, B., Eswarakumar, V. P., Zhang, J., Wang, F., & Bates, C. M.

citation count

  • 31

complete list of authors

  • Sims-Lucas, Sunder||Cusack, Brian||Eswarakumar, Veraragavan P||Zhang, Jue||Wang, Fen||Bates, Carlton M

publication date

  • April 2011