Nuclear phosphatase PPM1G in cellular survival and neural development

Authors

  • William H. Foster,

    1. Molecular, Cellular and Integrated Physiology Program, University of California at Los Angeles, Los Angeles, California
    2. Division of Molecular Medicine, Department of Anesthesiology, Medicine and Physiology, University of California at Los Angeles, Los Angeles, California
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    • Authorship Contributions: WF and YW conceived and designed the experiments. WF, AL and CG aonducted the experiments. WF, AL, CG, JC and YW analyzed data WF AL CG JC YW. WF and YW wrote the manuscript.

  • Adam Langenbacher,

    1. Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, California
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    • Authorship Contributions: WF and YW conceived and designed the experiments. WF, AL and CG aonducted the experiments. WF, AL, CG, JC and YW analyzed data WF AL CG JC YW. WF and YW wrote the manuscript.

  • Chen Gao,

    1. Division of Molecular Medicine, Department of Anesthesiology, Medicine and Physiology, University of California at Los Angeles, Los Angeles, California
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    • Authorship Contributions: WF and YW conceived and designed the experiments. WF, AL and CG aonducted the experiments. WF, AL, CG, JC and YW analyzed data WF AL CG JC YW. WF and YW wrote the manuscript.

  • Jaunian Chen,

    1. Department of Molecular, Cell and Developmental Biology, University of California at Los Angeles, Los Angeles, California
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    • Authorship Contributions: WF and YW conceived and designed the experiments. WF, AL and CG aonducted the experiments. WF, AL, CG, JC and YW analyzed data WF AL CG JC YW. WF and YW wrote the manuscript.

  • Yibin Wang

    Corresponding author
    1. Division of Molecular Medicine, Department of Anesthesiology, Medicine and Physiology, University of California at Los Angeles, Los Angeles, California
    • Molecular, Cellular and Integrated Physiology Program, University of California at Los Angeles, Los Angeles, California
    Search for more papers by this author
    • Authorship Contributions: WF and YW conceived and designed the experiments. WF, AL and CG aonducted the experiments. WF, AL, CG, JC and YW analyzed data WF AL CG JC YW. WF and YW wrote the manuscript.


  • Competing Interests: The authors have declared no competing interest.

Correspondence to: Yibin Wang, Ph.D., Departments of Anesthesiology, Physiology and Medicine, BH-569, CHS, University of California, Los Angeles, CA 90095. E-mail: yibinwang@mednet.ucla.edu

Abstract

Background: PPM1G is a nuclear localized serine/threonine phosphatase implicated to be a regulator of chromatin remodeling, mRNA splicing, and DNA damage. However, its in vivo function is unknown. Results: Here we show that ppm1g expression is highly enriched in the central nervous system during mouse and zebrafish development. ppm1g−/− mice were embryonic lethal with incomplete penetrance after E12.5. Rostral defects, including neural tube and craniofacial defects were observed in ppm1g−/− embryos associated with increased cell death in the neural epithelium. In zebrafish, loss of ppm1g also led to neural defects with aberrant neural marker gene expression. Primary fibroblasts from ppm1g−/− embryos failed to grow without immortalization while immortalized ppm1g−/− fibroblasts had increased cell death upon oxidative and genotoxic stress when compared to wild type fibroblasts. Conclusions: Our in vivo and in vitro studies revealed a critical role for PPM1G in normal development and cell survival. Developmental Dynamics 242:1101–1109, 2013. © 2013 Wiley Periodicals, Inc.

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