Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.07.24.219493v1?rss=1

Authors: Damen, M., Soroka, E., Khatif, H., Kukat, C., Simons, B. D., Bazzi, H.

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 orientations of the basal keratinocyte progenitors. Here, we use centrosomes, that organize the mitotic spindle, to test whether cell division orientations and stratification are linked. Genetically ablating centrosomes from the developing epidermis led to the activation of the p53-, 53BP1- and USP28-dependent mitotic surveillance pathway causing a thinner epidermis and hair follicle arrest. Importantly, the centrosome/p53 double mutant keratinocyte progenitors significantly altered their division orientations without affecting epidermal stratification. Time-lapse imaging and tissue growth dynamic measurements suggested that early stratification is initiated by a burst in basal and suprabasal cell proliferation as well as cell delamination. The data provide insights for tissue homeostasis and hyperproliferative diseases that may recapitulate developmental programs.

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