The young and the restless: regulation of adult neurogenesis by Wnt signaling

Abstract

Wnt signaling plays a critical role in developmental and adult neurogenesis. In this issue of Cell Stem Cell, Jang et al. (2013) and Seib et al. (2013) show how age and neuronal activity regulate adult hippocampal neurogenesis by inhibiting or activating, respectively, distinct components of the Wnt signaling machinery.

Figure 1. Wnt antagonists inhibit adult hippocampal neurogenesis

Wnt protein binding of the Frizzled/LRP heteromeric receptor and downstream formation of the β-catenin TCF/LEF complex leads to subsequent transcriptional activation of target genes. Inhibition by dickkopf-1 (Dkk1) and secreted frizzled-related protein 3 (sFRP3) of Wnt signaling downregulates adult stem cell proliferation and neuronal maturation. Exercise or electroshock (ECS) mediated neuronal activity inhibits sFRP3 expression, allowing Wnt-Frizzled/LRP binding and activating adult radial glial-like stem cells. Conversely, Dkk1 expression increases with age, precluding formation of the Wnt receptor complex and leading to suppression of adult hippocampal neurogenesis.