Dynamics of AdultAxin2Cell Lineage Integration in Granule Neurons of the Dentate Gyrus

Abstract

AbstractThe Wnt pathway plays critical roles in neurogenesis. The expression ofAxin2is induced by Wnt/β-catenin signaling, making this gene a sensitive indicator of canonical Wnt activity. We employed pulse-chase genetic lineage tracing with theAxin2-CreERT2allele to follow the fate ofAxin2-positive cells in the adult hippocampal formation. We foundAxin2expressed in astrocytes, neurons and endothelial cells, as well as in the choroid plexus epithelia. Simultaneously with tamoxifen induction ofAxin2fate mapping, the dividing cells were marked with 5-ethynyl-2’-deoxyuridine (EdU). Tamoxifen induction resulted in significant increase of dentate gyrus granule cells three months later; however, none of these neurons contained EdU signal. Conversely, six months after the tamoxifen/EdU pulse-chase labeling, EdU-positive granule neurons were identified in each animal. Our data imply thatAxin2is expressed at several different stages of adult granule neuron differentiation and suggest that the process of integration of the adult-born neurons from certain cell lineages may take longer than previously thought.