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

Author

Listed:
  • Masaji Sakaguchi

    (Institute of Molecular Embryology and Genetics, Kumamoto University
    Graduate School of Medical Sciences, 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)

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.

Suggested Citation

  • Masaji Sakaguchi & Sazia Sharmin & Atsuhiro Taguchi & Tomoko Ohmori & Sayoko Fujimura & Takaya Abe & Hiroshi Kiyonari & Yoshihiro Komatsu & Yuji Mishina & Makoto Asashima & Eiichi Araki & Ryuichi Nish, 2013. "The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth," Nature Communications, Nature, vol. 4(1), pages 1-10, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2408
    DOI: 10.1038/ncomms2408
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    Cited by:

    1. Zhe Ji & Wing-Yan Skyla Siu & Maria Emilia Dueñas & Leonie Müller & Matthias Trost & Pedro Carvalho, 2025. "Suppression of TGF-β/SMAD signaling by an inner nuclear membrane phosphatase complex," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    2. Zaili Luo & Dazhuan Xin & Yunfei Liao & Kalen Berry & Sean Ogurek & Feng Zhang & Liguo Zhang & Chuntao Zhao & Rohit Rao & Xinran Dong & Hao Li & Jianzhong Yu & Yifeng Lin & Guoying Huang & Lingli Xu &, 2023. "Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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