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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Glial Cell Line-Derived Neurotrophic Factor / genetics*
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Glial Cell Line-Derived Neurotrophic Factor / metabolism
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Kidney / growth & development*
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Mice
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Mice, Knockout
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Morphogenesis / genetics*
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Proto-Oncogene Proteins c-ets / genetics*
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Proto-Oncogene Proteins c-ets / metabolism
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Proto-Oncogene Proteins c-ret / genetics*
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Proto-Oncogene Proteins c-ret / metabolism
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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Etv4 protein, mouse
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Etv5 protein, mouse
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Glial Cell Line-Derived Neurotrophic Factor
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Proto-Oncogene Proteins c-ets
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Transcription Factors
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Proto-Oncogene Proteins c-ret
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Ret protein, mouse