The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth

Masaji Sakaguchi, Sazia Sharmin, Atsuhiro Taguchi, Tomoko Ohmori, Sayoko Fujimura, Takaya Abe, Hiroshi Kiyonari, Yoshihiro Komatsu, Yuji Mishina, Makoto Asashima, Eiichi Araki and Ryuichi Nishinakamura ()
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Masaji Sakaguchi: Institute of Molecular Embryology and Genetics, Kumamoto University
Sazia Sharmin: Institute of Molecular Embryology and Genetics, Kumamoto University
Atsuhiro Taguchi: Institute of Molecular Embryology and Genetics, Kumamoto University
Tomoko Ohmori: Institute of Molecular Embryology and Genetics, Kumamoto University
Sayoko Fujimura: Liaison Laboratory Promotion Facility, Institute of Molecular Embryology and Genetics, Kumamoto University
Takaya Abe: Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology (CDB), RIKEN Kobe
Hiroshi Kiyonari: Laboratory for Animal Resources and Genetic Engineering, Center for Developmental Biology (CDB), RIKEN Kobe
Yoshihiro Komatsu: School of Dentistry, University of Michigan
Yuji Mishina: School of Dentistry, University of Michigan
Makoto Asashima: Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology
Eiichi Araki: Graduate School of Medical Sciences, Kumamoto University
Ryuichi Nishinakamura: Institute of Molecular Embryology and Genetics, Kumamoto University

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract Most kidney nephron components, including glomeruli and renal tubules, derive from the metanephric mesenchyme. The overall differentiation into each component finishes at birth, but the molecular events linking the perinatal and adult kidneys remain elusive. Dullard was cloned from Xenopus kidneys, and encodes a phosphatase that negatively regulates BMP signalling. Here we report that Dullard deletion in the murine metanephric mesenchyme leads to failure of nephron maintenance after birth, resulting in lethality before adulthood. The nephron components are lost by massive apoptosis within 3 weeks after birth, leading to formation of a large hollow with a thin-layered cortex and medulla. Phosphorylated Smad1/5/8 is upregulated in the mutant nephrons, probably through cell-autonomous inhibitory effects of Dullard on BMP signalling. Importantly, administration of the BMP receptor kinase inhibitor LDN-193189 partially rescued the defects caused by Dullard deletion. Thus, Dullard keeps BMP signalling at an appropriate level, which is required for nephron maintenance in the postnatal period.

Date: 2013
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DOI: 10.1038/ncomms2408

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