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β-catenin mediates stress resilience through Dicer1/microRNA regulation

Author

Listed:
  • Caroline Dias

    (Icahn School of Medicine at Mount Sinai)

  • Jian Feng

    (Icahn School of Medicine at Mount Sinai)

  • Haosheng Sun

    (Icahn School of Medicine at Mount Sinai)

  • Ning yi Shao

    (Icahn School of Medicine at Mount Sinai)

  • Michelle S. Mazei-Robison

    (Icahn School of Medicine at Mount Sinai
    Present addresses: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA (M.S.M.-R.); Department of Psychology, UCLA College of Life Sciences, Los Angeles, California 90095, USA (P.K.); Institut National de la Santé et de la Recherche Médicale (INSERM) U1130; CNRS UMR8246; UPMC UM18, Neuroscience Paris Seine, 75005 Paris, France (V.V.); Department of Basic Medical Sciences, The University of Arizona College of Medicine-Phoenix, Arizona 85004, USA (D.F.).)

  • Diane Damez-Werno

    (Icahn School of Medicine at Mount Sinai)

  • Kimberly Scobie

    (Icahn School of Medicine at Mount Sinai)

  • Rosemary Bagot

    (Icahn School of Medicine at Mount Sinai)

  • Benoit LaBonté

    (Icahn School of Medicine at Mount Sinai)

  • Efrain Ribeiro

    (Icahn School of Medicine at Mount Sinai)

  • XiaoChuan Liu

    (Icahn School of Medicine at Mount Sinai)

  • Pamela Kennedy

    (Icahn School of Medicine at Mount Sinai
    Present addresses: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA (M.S.M.-R.); Department of Psychology, UCLA College of Life Sciences, Los Angeles, California 90095, USA (P.K.); Institut National de la Santé et de la Recherche Médicale (INSERM) U1130; CNRS UMR8246; UPMC UM18, Neuroscience Paris Seine, 75005 Paris, France (V.V.); Department of Basic Medical Sciences, The University of Arizona College of Medicine-Phoenix, Arizona 85004, USA (D.F.).)

  • Vincent Vialou

    (Icahn School of Medicine at Mount Sinai
    Present addresses: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA (M.S.M.-R.); Department of Psychology, UCLA College of Life Sciences, Los Angeles, California 90095, USA (P.K.); Institut National de la Santé et de la Recherche Médicale (INSERM) U1130; CNRS UMR8246; UPMC UM18, Neuroscience Paris Seine, 75005 Paris, France (V.V.); Department of Basic Medical Sciences, The University of Arizona College of Medicine-Phoenix, Arizona 85004, USA (D.F.).)

  • Deveroux Ferguson

    (Icahn School of Medicine at Mount Sinai
    Present addresses: Department of Physiology, Michigan State University, East Lansing, Michigan 48824, USA (M.S.M.-R.); Department of Psychology, UCLA College of Life Sciences, Los Angeles, California 90095, USA (P.K.); Institut National de la Santé et de la Recherche Médicale (INSERM) U1130; CNRS UMR8246; UPMC UM18, Neuroscience Paris Seine, 75005 Paris, France (V.V.); Department of Basic Medical Sciences, The University of Arizona College of Medicine-Phoenix, Arizona 85004, USA (D.F.).)

  • Catherine Peña

    (Icahn School of Medicine at Mount Sinai)

  • Erin S. Calipari

    (Icahn School of Medicine at Mount Sinai)

  • Ja Wook Koo

    (Icahn School of Medicine at Mount Sinai)

  • Ezekiell Mouzon

    (Icahn School of Medicine at Mount Sinai)

  • Subroto Ghose

    (University of Texas Southwestern)

  • Carol Tamminga

    (University of Texas Southwestern)

  • Rachael Neve

    (Massachusetts Institute of Technology)

  • Li Shen

    (Icahn School of Medicine at Mount Sinai)

  • Eric J. Nestler

    (Icahn School of Medicine at Mount Sinai)

Abstract

β-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice β-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide β-catenin enrichment mapping, we identify Dicer1—important in small RNA (for example, microRNA) biogenesis—as a β-catenin target gene that mediates resilience. Small RNA profiling after excising β-catenin from nucleus accumbens in the context of chronic stress reveals β-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish β-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.

Suggested Citation

  • Caroline Dias & Jian Feng & Haosheng Sun & Ning yi Shao & Michelle S. Mazei-Robison & Diane Damez-Werno & Kimberly Scobie & Rosemary Bagot & Benoit LaBonté & Efrain Ribeiro & XiaoChuan Liu & Pamela Ke, 2014. "β-catenin mediates stress resilience through Dicer1/microRNA regulation," Nature, Nature, vol. 516(7529), pages 51-55, December.
    • Handle: RePEc:nat:nature:v:516:y:2014:i:7529:d:10.1038_nature13976
    DOI: 10.1038/nature13976
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