TCF/Lef1-Mediated Control of Lipid Metabolism Regulates Skin Barrier Function

The study demonstrated that TCF/Lef1 signaling was crucial for skin barrier function by regulating lipid metabolism in the epidermis. In Lef1 mutant mice, altered signaling led to severe skin barrier impairment and early postnatal death, despite normal tight-junction formation. This defect was linked to changes in lipid composition and abnormalities in lipid lamellae assembly, with enzymes like Elovl3 and SCD1 being key targets. The study highlighted that impaired keratinocyte differentiation and lipid metabolism were central to the barrier defects, suggesting that TCF/Lef1 played a significant role in epidermal differentiation and lipid regulation, with implications for understanding human skin barrier diseases.