Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud

Haotian Zhao, Heather Kegg, Sandy Grady, Hoang Trang Truong, Michael L. Robinson, Michel Baum, Carlton M. Bates

Research output: Contribution to journalArticle

161 Scopus citations

Abstract

Fibroblast growth receptors (FGFRs) consist of four signaling family members. Mice with deletions of fgfr1 or fgfr2 are embryonic lethal prior to the onset of kidney development. To determine roles of FGFR1 and FGFR2 in the ureteric bud, we used a conditional targeting approach. First, we generated transgenic mice using the Hoxb7 promoter to drive cre recombinase and green fluorescent protein expression throughout ureteric bud tissue. We crossed Hoxb7creEGFP mice with mice carrying lox-p sites flanking critical regions of fgfr1 and/or fgfr2. Absence of fgfr1 from the ureteric bud (fgfr1 UB-/-) results in no apparent renal abnormalities. In contrast, fgfr2UB-/- mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2UB-/- ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr2UB-/- mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr2UB-/- kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr2UB-/- adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr1/2UB-/- kidneys versus the fgfr2UB-/- kidneys. In conclusion, FGFR2, but not FGFR1, appears crucial for ureteric bud branching morphogenesis and stromal mesenchyme patterning.

Original languageEnglish (US)
Pages (from-to)403-415
Number of pages13
JournalDevelopmental Biology
Volume276
Issue number2
DOIs
StatePublished - Dec 15 2004

Keywords

  • Branching morphogenesis
  • Conditional knockout
  • Fibroblast growth factor receptors
  • Kidney development
  • Stromal patterning
  • Ureteric bud

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Zhao, H., Kegg, H., Grady, S., Truong, H. T., Robinson, M. L., Baum, M., & Bates, C. M. (2004). Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Developmental Biology, 276(2), 403-415. https://doi.org/10.1016/j.ydbio.2004.09.002