Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme.
To determine the importance of fibroblast growth factor receptors (fgfrs) 1 and 2 in the metanephric mesenchyme, we generated conditional knockout mice (fgfr(Mes-/-)). Fgfr1(Mes-/-) and fgfr2(Mes-/-) mice develop normal-appearing kidneys. Deletion of both receptors (fgfr1/2(Mes-/-)) results in renal aplasia. Fgfr1/2(Mes-/-) mice develop a ureteric bud (and occasionally an ectopic bud) that does not elongate or branch, and the mice do not develop an obvious metanephric mesenchyme. By in situ hybridization, regions of mutant mesenchyme near the ureteric bud(s) express Eya1 and Six1, but not Six2, Sall1, or Pax2, while the ureteric bud expresses Ret and Pax2 normally. Abnormally high rates of apoptosis and relatively low rates of proliferation are present in mutant mesenchyme dorsal to the mutant ureteric bud at embryonic day (E) 10.5, while mutant ureteric bud tissues undergo high rates of apoptosis by E11.5. Thus, fgfr1 and fgfr2 together are critical for normal formation of metanephric mesenchyme. While the ureteric bud(s) initiates, it does not elongate or branch infgfr1/2(Mes-/-) mice. In metanephric mesenchymal rudiments, fgfr1 and fgfr2 appear to function downstream of Eya1 and Six1, but upstream of Six2, Sall1, and Pax2. Finally, this is the first example of renal aplasia in a conditional knockout model.
Poladia
Deepali Pitre
DP
Center for Cell and Vascular Biology, Columbus Children's Research Institute, 700 Children's Drive, Columbus, OH 43205, USA.
Kish
Kayle
K
Kutay
Benjamin
B
Hains
David
D
Kegg
Heather
H
Zhao
Haotian
H
Bates
Carlton M
CM
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000002:abnormalities / Q000196:embryology*; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000502:physiology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000502:physiology*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000502:physiology*
D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2