title: Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis.
abstract: 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.
authors.affiliation: Department of Genetics and Development, Columbia University Medical Center, New York, New York, USA.
authors.forename: Benson C
authors.initials: BC
authors.lastname: Lu
authors.forename: Cristina
authors.initials: C
authors.lastname: Cebrian
authors.forename: Xuan
authors.initials: X
authors.lastname: Chi
authors.forename: Satu
authors.initials: S
authors.lastname: Kuure
authors.forename: Richard
authors.initials: R
authors.lastname: Kuo
authors.forename: Carlton M
authors.initials: CM
authors.lastname: Bates
authors.forename: Silvia
authors.initials: S
authors.lastname: Arber
authors.forename: John
authors.initials: J
authors.lastname: Hassell
authors.forename: Lesley
authors.initials: L
authors.lastname: MacNeil
authors.forename: Masato
authors.initials: M
authors.lastname: Hoshi
authors.forename: Sanjay
authors.initials: S
authors.lastname: Jain
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kai M
authors.initials: KM
authors.lastname: Schmidt-Ott
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barasch
authors.forename: Vivette
authors.initials: V
authors.lastname: D'Agati
authors.forename: Frank
authors.initials: F
authors.lastname: Costantini
mesh_terms: 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
chemical_list: 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