High proliferation and delamination during skin epidermal stratification


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Authors
Damen, Mareike 
Soroka, Ekaterina 
Khatif, Houda 
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.

Description
Keywords
Article, /631/80/641, /631/80/128/1965, /631/80/128/1383, /631/136/2091, /631/208/135, /64/60, /14/19, /38/91, /82/1, /96/31, article
Journal Title
Nature Communications
Conference Name
Journal ISSN
2041-1723
Volume Title
12
Publisher
Nature Publishing Group UK
Sponsorship
Deutsche Forschungsgemeinschaft (German Research Foundation) (Project-ID 73111208, EXC 2030 – 390661388)