Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis.
Glial cell line-derived neurotrophic factor signaling through the Ret receptor tyrosine kinase is crucial for ureteric bud branching morphogenesis during kidney development, yet few of the downstream genes are known. Here we show that the ETS transcription factors Etv4 and Etv5 are positively regulated by Ret signaling in the ureteric bud tips. Mice lacking both Etv4 alleles and one Etv5 allele show either renal agenesis or severe hypodysplasia, whereas kidney development fails completely in double homozygotes. We identified several genes whose expression in the ureteric bud depends on Etv4 and Etv5, including Cxcr4, Myb, Met and Mmp14. Thus, Etv4 and Etv5 are key components of a gene network downstream of Ret that promotes and controls renal branching morphogenesis.
Lu
Benson C
BC
Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.
Cebrian
Cristina
C
Chi
Xuan
X
Kuure
Satu
S
Kuo
Richard
R
Bates
Carlton M
CM
Arber
Silvia
S
Hassell
John
J
MacNeil
Lesley
L
Hoshi
Masato
M
Jain
Sanjay
S
Asai
Naoya
N
Takahashi
Masahide
M
Schmidt-Ott
Kai M
KM
Barasch
Jonathan
J
D'Agati
Vivette
V
Costantini
Frank
F
D000818:Animals; D000831:Animals, Newborn; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C540571:Etv4 protein, mouse; C513242:Etv5 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse