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

December 2023 in “ The journal of investigative dermatology/Journal of investigative dermatology ”

Jyoti Prabha Satta, Qiang Lan, Makoto Mark Taketo, Marja L. Mikkola

β-catenin Wnt/β-catenin pathway hair follicle development mammary gland development mammary bud branching morphogenesis epidermal differentiation genes skin appendage identities beta-catenin Wnt signaling pathway hair follicle mammary gland branching epidermal differentiation skin appendages

Studysummary This study found that manipulating Wnt/β-catenin signaling in embryonic mammary glands impacted their development, with high activity levels hindering branching and potentially redirecting cells toward hair follicle identity instead of mammary tissue.

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The study investigates the role of the Wnt/β-catenin pathway in the development of mammary glands and hair follicles. It was found that while this pathway is crucial for the initiation of hair follicle and mammary gland development, its activity significantly decreases as the mammary bud progresses to branching. Forced activation of β-catenin compromises embryonic mammary gland branching, but a low level of Wnt/β-catenin activity is necessary for mammary cell survival. High β-catenin activity maintains the mammary bud gene signature at the expense of the outgrowth/branching gene signature and upregulates epidermal differentiation genes. Interestingly, early stabilization of β-catenin results in a partial switch to hair follicle fate, suggesting that the level of Wnt/β-catenin signaling activity may contribute to the choice between skin appendage identities.

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research Activation of Beta-Catenin Signaling Programs Embryonic Epidermis to Hair Follicle Fate

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