Disease relevance of Axin2

• Conductin is up-regulated during mitosis, localizes along the mitotic spindles of colon cancer cells, and binds to polo-like kinase 1 [1].
• Inhibition of Wnt signaling by a dominant-negative mutant of TCF downregulated conductin but not the related protein, axin, in DLD1 colorectal tumor cells [2].

High impact information on Axin2

• Here we demonstrate that Wnt/beta-catenin signaling causes CIN via up-regulation of conductin [1].
• Knock-down of conductin by small interfering RNA in colon carcinoma cells or gene ablation in mouse embryo fibroblasts enforces the checkpoint [1].
• Mouse axin and axin2/conductin proteins are functionally equivalent in vivo [3].
• Both Axin(Ax/Ax) and Axin(Ax2/Ax2) homozygotes are apparently normal and fertile, demonstrating that the Axin and Axin2 proteins are functionally equivalent [3].
• The 5.6-kb genomic sequence was sufficient to direct the tissue-specific expression of d2EGFP in transgenic embryos, consistent with a role for the Tcf/LEF sites and surrounding conserved sequences in the in vivo expression pattern of Axin2 [4].

Biological context of Axin2

• While Axin is expressed ubiquitously, Axin2 mRNA was seen in a restricted pattern during mouse embryogenesis and organogenesis [4].
• The role of Axin2 in calvarial morphogenesis and craniosynostosis [5].
• Targeted disruption of Axin2 in mice induces malformations of skull structures, a phenotype resembling craniosynostosis in humans [5].
• To further investigate the role of Wnt signaling during early neural development, and its potential regulation by Axins, we developed a mouse model for conditional gene activation in the Axin2-expressing domains [6].
• We show that gene expression can be successfully targeted to the Axin2-expressing cells in a spatially and temporally specific fashion [6].

Anatomical context of Axin2

• The calvarial osteoblast development is significantly affected by the Axin2 mutation [5].
• Furthermore, as the mammalian skull is formed from cranial skeletogenic mesenchyme, which is derived from mesoderm and neural crest, our data argue for a region-specific effect of Axin2 on neural crest dependent skeletogenesis [5].
• We show that Axin2 is expressed in the osteogenic fronts and periosteum of developing sutures during skull morphogenesis [5].
• Dact1 presomitic mesoderm expression oscillates in phase with Axin2 in the somitogenesis clock of mice [7].
• We also provide evidence indicating that only dkk1 and dkk4, along with two other Wnt antagonists axin2 and wif1, but not dkk2 and dkk3, are involved in a feedback mechanism to restrain Wnt signalling in transgenic mice carrying a conditional augmentation of beta-catenin in the forebrain [8].

Analytical, diagnostic and therapeutic context of Axin2

• Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24 [9].

References