Role of fibroblast growth factor receptor 2 in kidney mesenchyme.
Conditional deletion of murine fibroblast growth factor receptors (Fgfrs) 1 and 2 in metanephric mesenchyme leads to renal agenesis with unbranched ureteric buds; however, there are occasionally two buds per nephric duct. Our goal was to determine whether conditional deletion of Fgfr1 or Fgfr2 alone resulted in multiple ureteric bud induction sites. Although deletion of Fgfr1 alone results in no abnormalities, loss of Fgfr2 often leads to multiple ureteric buds and anomalies including renal aplasia, misshaped kidneys, partially duplicated kidneys, duplicated ureters, and obstructed hydroureter. Deletion of Fgfr2 did not change expression domains of glial cell line-derived neurotrophic factor (GDNF), Robo2, bone morphogenetic protein 4, or Sprouty1, all of which regulate ureteric bud induction. Cultured Fgfr2 mutant nephric ducts were also not more sensitive to exogenous GDNF than controls. Whole mount in situ hybridization revealed that in mutant embryos, Fgfr2 was deleted from stromal cells around the nephric duct and ureteric bud base, which correlates well with the ureteric bud induction abnormalities. Thus, Fgfr2 is critical in ensuring that there is a single ureteric bud from the nephric duct. The plethora of later stage defects in Fgfr2 conditional knockouts is reminiscent of many human cases of genetic urogenital anomalies.
Hains
David
D
Center for Cell and Developmental Biology, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
Sims-Lucas
Sunder
S
Kish
Kayle
K
Saha
Monalee
M
McHugh
Kirk
K
Bates
Carlton M
CM
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D014513:Ureter / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology; D000097905:Roundabout Proteins
D048868:Adaptor Proteins, Signal Transducing; D055415:Bone Morphogenetic Protein 4; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008565:Membrane Proteins; D010750:Phosphoproteins; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D011971:Receptors, Immunologic; C525810:Bmp4 protein, mouse; C498888:Robo2 protein, mouse; D000097905:Roundabout Proteins; C425468:Spry1 protein, mouse