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High proliferation and delamination during skin epidermal stratification

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  • Mareike Damen

    (University Hospital of Cologne, University of Cologne
    University of Cologne
    University of Cologne)

  • Lisa Wirtz

    (University Hospital of Cologne, University of Cologne
    University of Cologne
    University of Cologne)

  • Ekaterina Soroka

    (University Hospital of Cologne, University of Cologne
    University of Cologne)

  • Houda Khatif

    (University Hospital of Cologne, University 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
    University of Cologne
    University of Cologne)

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.

Suggested Citation

  • Mareike Damen & Lisa Wirtz & Ekaterina Soroka & Houda Khatif & Christian Kukat & Benjamin D. Simons & Hisham Bazzi, 2021. "High proliferation and delamination during skin epidermal stratification," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23386-4
    DOI: 10.1038/s41467-021-23386-4
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