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 TammingaRachael Neve, Li Shen, Eric J. Nestler

Research output: Contribution to journalArticle

116 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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