Loss of peri-Wolffian duct stromal Frs2α expression in mice leads to abnormal ureteric bud induction and vesicoureteral reflux

Deepti Narla, Stacey B. Slagle, Caitlin M. Schaefer, Daniel S. Bushnell, Pawan Puri, Carlton M. Bates

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

BackgroundFibroblast growth factor receptor 2 (Fgfr2) deletion from murine peri-Wolffian duct stroma (ST) results in aberrant ureteric bud induction, abnormal ureteral insertion into the bladder, and high rates of vesicoureteral reflux (VUR). It is unclear which receptor docking protein(s) is/are responsible for Fgfr2 actions in these tissues. We investigated whether the docking protein, fibroblast receptor substrate 2α (Frs2α), had a role in peri-Wolffian duct ST similar to Fgfr2.MethodsWe conditionally deleted Frs2α in peri-Wolffian duct ST with a Tbx18cre mouse line (Frs2α ST-/-). We assessed for ureteric induction defects and alterations in downstream targets mediating defects. We performed euthanized cystograms and assessed ureter-bladder junctions by three-dimensional (3D) reconstructions.ResultsEmbryonic day (E) 11.5 Frs2α ST-/- embryos had many displaced ureteric bud induction sites when compared with controls. E11.0 Frs2α ST-/- embryos had decreased Bmp4 expression and signaling, which can cause abnormal ureteric bud induction. Postnatal day 1 (P1) and P30 Frs2α ST-/- mice had higher VUR rates and grades vs. Controls. Mutant refluxing ureters that inserted improperly into the bladder had shortened intravesicular tunnels (IVTs) when compared with controlsConclusionFrs2α ST-/- embryos have aberrant ureteric induction sites, improper ureteral insertion, shortened intravesicular lengths, and VUR. Induction site defects appear secondary to reduced Bmp4 expression, similar to Fgfr2 mutants.

Original languageEnglish (US)
Pages (from-to)1022-1029
Number of pages8
JournalPediatric Research
Volume82
Issue number6
DOIs
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this