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

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138 Scopus citations

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 languageEnglish
Pages (from-to)1295-1302
Number of pages8
JournalNature Genetics
Volume41
Issue number12
DOIs
StatePublished - Dec 1 2009

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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