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High proliferation and delamination during skin epidermal stratification

Mareike Damen, Lisa Wirtz, Ekaterina Soroka, Houda Khatif, Christian Kukat, Benjamin D. Simons and Hisham Bazzi ()
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Mareike Damen: University Hospital of Cologne, University of Cologne
Lisa Wirtz: University Hospital of Cologne, University of Cologne
Ekaterina Soroka: University Hospital of Cologne, University of Cologne
Houda Khatif: University Hospital of Cologne, University of Cologne
Christian Kukat: FACS & Imaging Core Facility, Max Planck Institute for Biology of Aging
Benjamin D. Simons: University of Cambridge
Hisham Bazzi: University Hospital of Cologne, University of Cologne

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract The development of complex stratified epithelial barriers in mammals is initiated from single-layered epithelia. How stratification is initiated and fueled are still open questions. Previous studies on skin epidermal stratification suggested a central role for perpendicular/asymmetric cell division orientation of the basal keratinocyte progenitors. Here, we use centrosomes, that organize the mitotic spindle, to test whether cell division orientation and stratification are linked. Genetically ablating centrosomes from the developing epidermis leads to the activation of the p53-, 53BP1- and USP28-dependent mitotic surveillance pathway causing a thinner epidermis and hair follicle arrest. The centrosome/p53-double mutant keratinocyte progenitors significantly alter their division orientation in the later stages without majorly affecting epidermal differentiation. Together with time-lapse imaging and tissue growth dynamics measurements, the data suggest that the first and major phase of epidermal development is boosted by high proliferation rates in both basal and suprabasally-committed keratinocytes as well as cell delamination, whereas the second phase maybe uncoupled from the division orientation of the basal progenitors. The data provide insights for tissue homeostasis and hyperproliferative diseases that may recapitulate developmental programs.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23386-4

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DOI: 10.1038/s41467-021-23386-4

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