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 & 3 others Rachael Neve, Li Shen, Eric J. Nestler

Research output: Contribution to journalArticle

110 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)51-55
Number of pages5
JournalNature
Volume516
Issue number7529
DOIs
StatePublished - Dec 4 2014

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Catenins
MicroRNAs
Nucleus Accumbens
RNA
Anti-Anxiety Agents
Reward
Central Nervous System
Genome
Depression
Neurons
Brain
Genes

ASJC Scopus subject areas

  • General

Cite this

Dias, C., Feng, J., Sun, H., Shao, N. Y., Mazei-Robison, M. S., Damez-Werno, D., ... Nestler, E. J. (2014). β-catenin mediates stress resilience through Dicer1/microRNA regulation. Nature, 516(7529), 51-55. https://doi.org/10.1038/nature13976

β-catenin mediates stress resilience through Dicer1/microRNA regulation. / Dias, Caroline; Feng, Jian; Sun, Haosheng; Shao, Ning Yi; Mazei-Robison, Michelle S.; Damez-Werno, Diane; Scobie, Kimberly; Bagot, Rosemary; LaBonté, Benoit; Ribeiro, Efrain; Liu, Xiaochuan; Kennedy, Pamela; Vialou, Vincent; Ferguson, Deveroux; Peña, Catherine; Calipari, Erin S.; Koo, Ja Wook; Mouzon, Ezekiell; Ghose, Subroto; Tamminga, Carol; Neve, Rachael; Shen, Li; Nestler, Eric J.

In: Nature, Vol. 516, No. 7529, 04.12.2014, p. 51-55.

Research output: Contribution to journalArticle

Dias, C, Feng, J, Sun, H, Shao, NY, Mazei-Robison, MS, Damez-Werno, D, Scobie, K, Bagot, R, LaBonté, B, Ribeiro, E, Liu, X, Kennedy, P, Vialou, V, Ferguson, D, Peña, C, Calipari, ES, Koo, JW, Mouzon, E, Ghose, S, Tamminga, C, Neve, R, Shen, L & Nestler, EJ 2014, 'β-catenin mediates stress resilience through Dicer1/microRNA regulation', Nature, vol. 516, no. 7529, pp. 51-55. https://doi.org/10.1038/nature13976
Dias C, Feng J, Sun H, Shao NY, Mazei-Robison MS, Damez-Werno D et al. β-catenin mediates stress resilience through Dicer1/microRNA regulation. Nature. 2014 Dec 4;516(7529):51-55. https://doi.org/10.1038/nature13976
Dias, Caroline ; Feng, Jian ; Sun, Haosheng ; Shao, Ning Yi ; Mazei-Robison, Michelle S. ; Damez-Werno, Diane ; Scobie, Kimberly ; Bagot, Rosemary ; LaBonté, Benoit ; Ribeiro, Efrain ; Liu, Xiaochuan ; Kennedy, Pamela ; Vialou, Vincent ; Ferguson, Deveroux ; Peña, Catherine ; Calipari, Erin S. ; Koo, Ja Wook ; Mouzon, Ezekiell ; Ghose, Subroto ; Tamminga, Carol ; Neve, Rachael ; Shen, Li ; Nestler, Eric J. / β-catenin mediates stress resilience through Dicer1/microRNA regulation. In: Nature. 2014 ; Vol. 516, No. 7529. pp. 51-55.
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AU - Shen, Li

AU - Nestler, Eric J.

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