β-catenin mediates stress resilience through Dicer1/microRNA regulation

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 Kennedy, Vincent Vialou, Deveroux Ferguson, Catherine Peña, Erin S. Calipari, Ja Wook Koo, Ezekiell Mouzon, Subroto Ghose, Carol Tamminga, Rachael Neve, Li Shen () and Eric J. Nestler ()
Additional contact information
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
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
Vincent Vialou: Icahn School of Medicine at Mount Sinai
Deveroux Ferguson: Icahn School of Medicine at Mount Sinai
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

Nature, 2014, vol. 516, issue 7529, 51-55

Abstract: 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.

Date: 2014
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DOI: 10.1038/nature13976

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