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High proliferation and delamination during skin epidermal stratification.

Published version
Peer-reviewed

Type

Article

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Authors

Damen, Mareike 
Soroka, Ekaterina 
Khatif, Houda 

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

Adolescent, Adult, Aged, Animals, Asymmetric Cell Division, Cell Differentiation, Cell Proliferation, Centrosome, Child, Child, Preschool, Embryo, Mammalian, Epidermis, Female, Hair Follicle, Humans, Keratinocytes, Male, Mice, Mice, Knockout, Middle Aged, Models, Biological, Skin Physiological Phenomena, Spindle Apparatus, Time-Lapse Imaging, Tumor Suppressor Protein p53, Tumor Suppressor p53-Binding Protein 1, Ubiquitin Thiolesterase, Young Adult

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

12

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Wellcome Trust (219478/Z/19/Z)
Royal Society