Stabilization of Epithelial Beta-Catenin Compromises Mammary Cell Fate Acquisition and Branching Morphogenesis

The study investigates the role of the Wnt/β-catenin pathway in the development of mammary glands and hair follicles. It was found that as the mammary bud develops into branches, there is a significant reduction in epithelial Wnt/β-catenin activity. When β-catenin activity was artificially increased, embryonic mammary gland branching was severely hindered, indicating that a precise level of this activity is crucial for proper development. Although a low level of Wnt/β-catenin activity is necessary for mammary cell survival, as suggested by the phenotype of conditional Lef1 deficient embryos, high levels of β-catenin activity maintained a mammary bud gene signature and upregulated epidermal differentiation genes, at the expense of outgrowth and branching. Notably, the study also observed that high β-catenin activity induced a partial switch to hair follicle fate in the early stages, suggesting that the level of Wnt/β-catenin signaling contributes to determining the identity of skin appendages.