β-catenin mediates stress resilience through Dicer1/microRNA regulation

Academic Article

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.
  • Authors

    Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Dias C; Feng J; Sun H; Shao NY; Mazei-Robison MS; Damez-Werno D; Scobie K; Bagot R; Labonté B; Ribeiro E
  • Start Page

  • S1
  • End Page

  • S5
  • Volume

  • 516
  • Issue

  • 729