Polarity Signaling Ensures Epidermal Homeostasis by Coupling Cellular Mechanics and Genomic Integrity

The study explored the role of the polarity protein Par3 in maintaining epidermal homeostasis by regulating cellular mechanics and genomic integrity in keratinocytes. It was found that Par3 is crucial for ensuring mitotic fidelity and genome integrity, as its deficiency led to impaired RhoA activity, mitotic failures, aneuploidy, and DNA damage, which triggered premature differentiation. The research demonstrated that restoring myosin activity could correct these defects, emphasizing the importance of Par3 in coupling mechanical forces with genomic stability to ensure balanced self-renewal and differentiation in the epidermis. The findings suggested that disruptions in this polarity signaling network could compromise epidermal and potentially other epithelial tissue homeostasis.