Together, our results demonstrated that knockdown of Wnt2 or Wnt3 in the VH could lead to depression-like behaviors, impaired Wnt/β-catenin signaling and decreased neurogenesis, which suggested that the induced depression-like behaviors may be the results of impaired Wnt/β-catenin signaling or decreased neurogenesis in the VH. The gene discussed is WNT2; the disease is major depressive disorder.