A Two-Phase Model of Skin Epidermal Stratification: Lessons from Centrosomes

    Mareike Damen, Lisa Wirtz, Ekaterina Soroka, Houda Khatif, Christian Kukat, Benjamin D. Simons, Hisham Bazzi
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    Studysummary This study found that centrosome ablation in developing epidermis triggers cell surveillance pathways, resulting in thinner skin and halted hair follicle growth, while later stages of epidermal growth may operate independently of basal progenitor division orientation.
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    The study investigated the initiation and progression of skin epidermal stratification, focusing on the role of cell division orientation in basal keratinocyte progenitors. Researchers genetically removed centrosomes, which organize the mitotic spindle, from developing epidermis and observed the activation of a mitotic surveillance pathway involving p53, 53BP1, and USP28, resulting in a thinner epidermis and halted hair follicle development. Despite changes in division orientation in centrosome/p53-double mutant keratinocyte progenitors during later stages, epidermal differentiation was not significantly affected. Time-lapse imaging and tissue growth dynamics measurements indicated that the initial phase of epidermal stratification is driven by high proliferation rates of basal and suprabasal transit-amplifying cells and cell delamination, while the second phase may not depend on the division orientation of basal progenitors. This research provides insights into tissue homeostasis and diseases characterized by hyperproliferation, which may mimic developmental processes.
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