Repository logo
 

High proliferation and delamination during skin epidermal stratification.

Published version
Peer-reviewed

Type

Article

Change log

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

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

Journal Title

Nature communications

Conference Name

Journal ISSN

2041-1723

Volume Title

12

Publisher

Sponsorship
Wellcome Trust (219478/Z/19/Z)