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

157 Citations (Scopus)

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, fgfr2 UB-/- mice have very aberrant ureteric bud branching, thin ureteric bud stalks, and fewer ureteric bud tips. Fgfr2 UB-/- ureteric bud tips also demonstrate inappropriate regions of apoptosis and reduced proliferation. The nephrogenic mesenchymal lineage in fgfr2 UB-/- mice develops normal-appearing glomeruli and tubules, and only slightly fewer nephrons than controls. In contrast, fgfr2 UB-/- kidneys have abnormally thickened subcapsular cortical stromal mesenchyme. Ultimately, fgfr2 UB-/- adult kidneys are small and abnormally shaped or are hydronephrotic. Finally, there are no additional abnormalities in the fgfr1/2 UB-/- kidneys versus the fgfr2 UB-/- 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

Fingerprint

Receptor, Fibroblast Growth Factor, Type 2
Receptor, Fibroblast Growth Factor, Type 1
Kidney
Mesoderm
Nephrons
Green Fluorescent Proteins
Morphogenesis
Transgenic Mice
Fibroblasts
Apoptosis
Growth

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology

Cite this

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

Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. / Zhao, Haotian; Kegg, Heather; Grady, Sandy; Truong, Hoang Trang; Robinson, Michael L.; Baum, Michel; Bates, Carlton M.

In: Developmental Biology, Vol. 276, No. 2, 15.12.2004, p. 403-415.

Research output: Contribution to journalArticle

Zhao, H, Kegg, H, Grady, S, Truong, HT, Robinson, ML, Baum, M & Bates, CM 2004, 'Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud', Developmental Biology, vol. 276, no. 2, pp. 403-415. https://doi.org/10.1016/j.ydbio.2004.09.002
Zhao, Haotian ; Kegg, Heather ; Grady, Sandy ; Truong, Hoang Trang ; Robinson, Michael L. ; Baum, Michel ; Bates, Carlton M. / Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. In: Developmental Biology. 2004 ; Vol. 276, No. 2. pp. 403-415.
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