Independent roles of Fgfr2 and Frs2α in ureteric epithelium

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

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Mice with conditional deletion of fibroblast growth factor receptor 2 (Fgfr2) in the ureteric bud using a Hoxb7cre line (Fgfr2UB-/-) 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 (Frs2αUB-/-) leads to mild ureteric defects. Mice with point mutations in the Frs2α binding site of Fgfr2 (Fgfr2LR/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/Frs2αUB-/) were compared with Frs2αUB-/- and Fgfr2UB-/- mice. To avoid potential rescue of Fgfr1 forming heterodimers with Fgfr2LR alleles to recruit Frs2α, compound mutant mice were generated with ureteric deletion of Fgfr1 and with Fgfr2LR/LR point mutations (Fgfr1UB-/-Fgfr2LR/LR). At E13.5, three-dimensional reconstructions and histological assessment showed that, whereas Fgfr2UB-/- kidneys had more severe ureteric branching defects than Frs2αUB-/-, Fgfr2UB-/- kidneys were indistinguishable from Fgfr2/Frs2αUB-/-. At later stages, however, Fgfr2/Frs2αUB-/- kidneys were more severely affected than either Fgfr2UB-/- or Frs2αUB-/- kidneys. Taken together, although Fgfr2 and Frs2α have crucial roles in the ureteric lineage, they appear to act separately and additively.

Original languageEnglish (US)
Pages (from-to)1275-1280
Number of pages6
JournalDevelopment
Volume138
Issue number7
DOIs
StatePublished - Apr 2011
Externally publishedYes

Keywords

  • Fibroblast growth factor receptor 2
  • Frs2α
  • Mouse
  • Ureteric epithelium

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Fingerprint Dive into the research topics of 'Independent roles of Fgfr2 and Frs2α in ureteric epithelium'. Together they form a unique fingerprint.

Cite this