High proliferation and delamination during skin epidermal stratification

Area of Science:

• Developmental Biology
• Cell Biology
• Epithelial Biology

Background:

• Mammalian stratified epithelial barriers develop from single-layered epithelia.
• The initiation and drivers of epidermal stratification remain incompletely understood.
• Previous research implicated basal keratinocyte progenitor cell division orientation in skin epidermal stratification.

Purpose of the Study:

• To investigate the link between cell division orientation and epidermal stratification using centrosomes.
• To elucidate the role of centrosomes in epidermal development and stratification.

Main Methods:

• Genetic ablation of centrosomes in developing epidermis.
• Analysis of the p53, 53BP1, and USP28 mitotic surveillance pathway.
• Time-lapse imaging and tissue growth dynamics measurements.
• Assessment of keratinocyte progenitor cell division orientation and epidermal differentiation.

Main Results:

• Centrosome ablation activated the p53-dependent mitotic surveillance pathway, resulting in thinner epidermis and hair follicle arrest.
• Centrosome/p53-double mutant keratinocyte progenitors showed altered division orientation in later stages without significantly impacting epidermal differentiation.
• Epidermal development's initial phase is driven by high proliferation and cell delamination, while the second phase may be independent of basal progenitor division orientation.

Conclusions:

• Centrosome function is critical for normal epidermal development and stratification.
• Cell division orientation of basal progenitors is not the primary driver for all stages of epidermal stratification.
• Findings offer insights into tissue homeostasis and hyperproliferative diseases potentially mimicking developmental processes.