# Exploring the dynamics of adult Axin2 cell lineage integration into dentate gyrus granule neurons

## TL;DR

This study shows that Axin2+ cells in the adult brain can become dentate gyrus neurons, but the process takes at least six months.

## Contribution

The study reveals a novel timeline for Axin2+ lineage integration into adult neurons in the hippocampus.

## Key findings

- Axin2 is expressed in multiple cell types, including astrocytes, neurons, and endothelial cells.
- Granule neurons positive for both tdTomato and EdU were identified six months after labeling.
- The integration of Axin2+ lineage into neurons may take longer than previously assumed.

## Abstract

The Wnt pathway plays critical roles in neurogenesis. The expression of Axin2 is induced by Wnt/β-catenin signaling, making this gene a reliable indicator of canonical Wnt activity. We employed pulse-chase genetic lineage tracing with the Axin2-CreERT2 allele to follow the fate of Axin2+ lineage in the adult hippocampal formation. We found Axin2 expressed in astrocytes, neurons and endothelial cells, as well as in the choroid plexus epithelia. Simultaneously with the induction of Axin2 fate mapping by tamoxifen, we marked the dividing cells with 5-ethynyl-2′-deoxyuridine (EdU). Tamoxifen induction led to a significant increase in labeled dentate gyrus granule cells three months later. However, none of these neurons showed any EdU signal. Conversely, six months after the pulse-chase labeling with tamoxifen/EdU, we identified granule neurons that were positive for both EdU and tdTomato lineage tracer in each animal. Our data indicates that Axin2 is expressed at multiple stages of adult granule neuron differentiation. Furthermore, these findings suggest that the integration process of adult-born neurons from specific cell lineages may require more time than previously thought.