Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis

Benson C. Lu; Cristina Cebrian; Xuan Chi; Satu Kuure; Richard Kuo; Carlton M. Bates; Silvia Arber; John Hassell; Lesley MacNeil; Masato Hoshi; Sanjay Jain; Naoya Asai; Masahide Takahashi; Kai M. Schmidt-Ott; Jonathan Barasch; Vivette D'Agati; Frank Costantini

doi:10.1038/ng.476

Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis

Benson C. Lu, Cristina Cebrian, Xuan Chi, Satu Kuure, Richard Kuo, Carlton M. Bates, Silvia Arber, John Hassell, Lesley MacNeil, Masato Hoshi, Sanjay Jain, Naoya Asai, Masahide Takahashi, Kai M. Schmidt-Ott, Jonathan Barasch, Vivette D'Agati, Frank Costantini

Research output: Contribution to journal › Article › peer-review

183 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1295-1302
Number of pages	8
Journal	Nature Genetics
Volume	41
Issue number	12
DOIs	https://doi.org/10.1038/ng.476
Publication status	Published - 12-2009
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

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Lu, B. C., Cebrian, C., Chi, X., Kuure, S., Kuo, R., Bates, C. M., Arber, S., Hassell, J., MacNeil, L., Hoshi, M., Jain, S., Asai, N., Takahashi, M., Schmidt-Ott, K. M., Barasch, J., D'Agati, V., & Costantini, F. (2009). Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nature Genetics, 41(12), 1295-1302. https://doi.org/10.1038/ng.476

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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.",

author = "Lu, {Benson C.} and Cristina Cebrian and Xuan Chi and Satu Kuure and Richard Kuo and Bates, {Carlton M.} and Silvia Arber and John Hassell and Lesley MacNeil and Masato Hoshi and Sanjay Jain and Naoya Asai and Masahide Takahashi and Schmidt-Ott, {Kai M.} and Jonathan Barasch and Vivette D'Agati and Frank Costantini",

note = "Funding Information: WethankS.Simonet(Amgen)forFgf10−/−mice,K.Murphy(Washington University) for Etv5tm1Kmm mice, L. Williams and Z. Wu for technical assistance and N. Kurpios and C. Mendelsohn for critical comments on the manuscript. This work was supported by grant DK55388 (to F.C. and J.B.) and grant DK075578 (to F.C.) and by fellowships from the National Kidney Foundation (to C.C.), the American Heart Association (to X.C.) and the Sigrid Juselius Foundation and Finnish Cultural Foundation (to S.K.).",

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AU - Kuo, Richard

AU - Bates, Carlton M.

AU - Arber, Silvia

AU - Hassell, John

AU - MacNeil, Lesley

AU - Hoshi, Masato

AU - Jain, Sanjay

AU - Asai, Naoya

AU - Takahashi, Masahide

AU - Schmidt-Ott, Kai M.

AU - Barasch, Jonathan

AU - D'Agati, Vivette

AU - Costantini, Frank

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N2 - 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.

AB - 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.

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Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis

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