β-catenin mediates stress resilience through Dicer1/microRNA regulation

Caroline Dias, Jian Feng, Haosheng Sun, Ning Y.i. Shao, Michelle S. Mazei-Robison, Diane Damez-Werno, Kimberly Scobie, Rosemary Bagot, Benoit LaBonté, Efrain Ribeiro, Xiao Chuan Liu, Pamela Kennedy, Vincent Vialou, Deveroux Ferguson, Catherine Peña, Erin S. Calipari, Ja W.ook Koo, Ezekiell Mouzon, Subroto Ghose, Carol TammingaRachael Neve, Li Shen, Eric J. Nestler

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120 Scopus citations

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)S1-S5
JournalNature
Volume516
Issue number729
DOIs
StatePublished - Dec 4 2014

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ASJC Scopus subject areas

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Cite this

Dias, C., Feng, J., Sun, H., Shao, N. Y. I., Mazei-Robison, M. S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonté, B., Ribeiro, E., Liu, X. C., Kennedy, P., Vialou, V., Ferguson, D., Peña, C., Calipari, E. S., Koo, J. W. O., Mouzon, E., Ghose, S., ... Nestler, E. J. (2014). β-catenin mediates stress resilience through Dicer1/microRNA regulation. Nature, 516(729), S1-S5. https://doi.org/10.1038/nature13976