Of Mice and Skin: Investigating the Role of E-Cadherin in Murine Epidermal Stem Cell Division Orientation

Abstract

Epidermal basal stem cells balance renewal and differentiation through symmetric and asymmetric divisions to maintain their population while generating proper skin morphology and function. An imbalance in either of these processes can result in cancer and tissue degeneration. Despite these implications, the mechanisms regulating stem cell division orientation in the skin remain largely unknown. However, recent research showing that basal stem cells change their proliferative behavior in response to feedback from differentiated daughter cells of the suprabasal layer provides insight. Therefore, in this research, I elucidate the role of mechanosensitive adherens junctions between basal and suprabasal cells in regulating basal stem cell division orientation. Using immunofluorescence to assess skin morphology and basal cell division in E-cadherin knockout mice, I find that loss of E-cadherin within basal cells results in a loss of apical adherens junctions, preventing basal cells from being able to receive extrinsic feedback from their direct-contact suprabasal daughters. Unaware of whether the stratified layers require repopulation, basal cells lacking E-cadherin expression proportionally increase perpendicular divisions. Therefore, this research establishes a novel role of E-cadherin- based adherens junctions in communicating a need for basal cell division of a specific orientation. Overall, the findings of this research expand scientific understanding of the core processes behind normal and atypical development of the skin.