Dynamics of Adult Axin2 Cell Lineage Integration in Granule Neurons of the Dentate Gyrus

The Wnt pathway plays critical roles in neurogenesis. The expression of Axin2 is induced by Wnt/β-catenin signaling, making this gene a sensitive indicator of canonical Wnt activity. We employed pulse-chase genetic lineage tracing with the Axin2-CreERT2 allele to follow the fate of Axin2-positive cells 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 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 and suggest that the process of integration of the adult-born neurons from certain cell lineages may take longer than previously thought.

Wnt通路在神经发生中起关键作用。Axin2的表达由Wnt/β -连环蛋白信号传导诱导，使得该基因成为经典Wnt活性的敏感指标。我们使用Axin2 - CreERT2等位基因进行脉冲追踪遗传谱系追踪，以追踪成年海马结构中Axin2阳性细胞的命运。我们发现Axin2在星形胶质细胞、神经元和内皮细胞以及脉络丛上皮细胞中表达。在他莫昔芬诱导Axin2命运图谱的同时，分裂细胞用5 - 乙炔基 - 2’ - 脱氧尿苷（EdU）标记。他莫昔芬诱导在三个月后导致齿状回颗粒细胞显著增加；然而，这些神经元中没有一个含有EdU信号。相反，在他莫昔芬/EdU脉冲追踪标记六个月后，在每只动物中都鉴定出EdU阳性颗粒神经元。我们的数据表明Axin2在成年颗粒神经元分化的几个不同阶段表达，并提示来自某些细胞谱系的成年新生神经元的整合过程可能比以前认为的要长。