Prolonged Integration of Adult-Born Axin2 Cell Lineage Into Granule Neurons of the Dentate Gyrus

Abstract

The Wnt pathway plays many roles during adult neurogenesis. The expression of Axin2 is induced by Wnt/β-catenin signaling, making this gene a sensitive indicator of canonical Wnt activity. We have employed pulse-chase genetic lineage tracing with the Axin2-CreER allele to follow the fate of Axin2-positive cells in the hippocampus. Simultaneously with tamoxifen induction of Axin2 fate 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 that Axin2 is expressed at several different stages of adult granule neuron differentiation, including in the dividing neural stem cells. In addition, our data indicate that the process of integration of the adult-born neurons from certain cell lineages may take longer than previously thought.

Funding Information: This work was supported in part with FUSF foundation seed grant and NIH grant R21NS116431 to P.T.

Declaration of Interests: The authors declare no competing financial interests.

Ethics Approval Statement: All animal experiments were approved by the IACUC at University of Virginia.

Keywords: adult neurogenesis, Neural Stem Cells, Wnt signaling, Axin2