Universität zu Köln

Damen, Mareike, Wirtz, Lisa ORCID: 0000-0001-9967-6729, Soroka, Ekaterina, Khatif, Houda, Kukat, Christian ORCID: 0000-0003-1508-0229, Simons, Benjamin D. and Bazzi, Hisham ORCID: 0000-0001-8388-4005 (2021). High proliferation and delamination during skin epidermal stratification. Nat. Commun., 12 (1). BERLIN: NATURE RESEARCH. ISSN 2041-1723

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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. How the developing skin epidermis is transformed from a simple single-layered epithelium to a complex and stratified barrier is still an open question. Here, the authors provide a model based on high proliferation and delamination of the keratinocyte progenitors that support the stratification process.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Damen, Mareike UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Lisa UNSPECIFIED orcid.org/0000-0001-9967-6729 UNSPECIFIED Soroka, Ekaterina UNSPECIFIED UNSPECIFIED UNSPECIFIED Khatif, Houda UNSPECIFIED UNSPECIFIED UNSPECIFIED Kukat, Christian UNSPECIFIED orcid.org/0000-0003-1508-0229 UNSPECIFIED Simons, Benjamin D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bazzi, Hisham UNSPECIFIED orcid.org/0000-0001-8388-4005 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-584289
DOI:	10.1038/s41467-021-23386-4
Journal or Publication Title:	Nat. Commun.
Volume:	12
Number:	1
Date:	2021
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ASYMMETRIC CELL DIVISIONS; MITOTIC SPINDLE ORIENTATION; CENTROSOME LOSS; PRIMARY CILIUM; DIFFERENTIATION; P53; GROWTH; HOMEOSTASIS; P63; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58428