(A) Structure of Negr1. Loops represent immunoglobulin-like domains. Lines ending with dots are putative N-linked glycosylation sites. (B) Schematic illustration of the molecular mechanism underlying the regulatory role of Negr1 in anxiety- and depressive-like behaviors. Negr1 interacts with LIF receptor and potentiates Lcn2 expression. Lcn2, in turn, induces hippocampal neurogenesis in adult mice. In negr1 ^−/− mice, impaired adult hippocampal neurogenesis due to reduced Lcn2 expression results in anxiety- and depression-like behaviors.