Function of the Wnt3 gene is required for mouse gastrulation

Gastrulation is the complex series of cell movements from which the axes and germ layers of the embryo emerge. Mutations in a number of genes perturb gastrulation with respect to cell movements and gene expression. Which genes are responsible for the initiation of gastrulation has been heretofore unknown. However, ectopic activation of the Wnt -signaling cascade in Xenopus laevis embryos has suggested that components of this pathway may have a central role in gastrulation. Presented in this dissertation are the results of disruption of the mouse Wnt3 gene by homologous recombination. Mice heterozygous for the Wnt3 mutation are normal and fertile. Contrastingly, mice that are homozygous for the Wnt3 mutation arrest in their developmental program at the egg cylinder-stage and eventually undergo necrosis. Wnt3 homozygotes display neither histological not molecular marker evidence of a primitive streak. The embryonic ectoderm is abnormally thickened in Wnt3 homozygotes, but exhibits a normal pattern of gene expression. Other tissues in the Wnt3 homozygotes, the extraembryonic ectoderm, the visceral endoderm, and the parietal endoderm, manifest normal histology and patterns of gene expression. There is a diminished rate of cell proliferation in embryos homozygous for the Wnt3 mutation. In conclusion, function of the Wnt3 gene appears to be a requisite for the initiation of gastrulation and formation of a primitive streak.