Abstract

Asymmetric cell divisions (ACDs) result in two unequal daughter cells and are a hallmark of stem cells. ACDs can be achieved either by asymmetric partitioning of proteins and organelles or by asymmetric cell fate acquisition due to the microenvironment in which the daughters are placed. Increasing evidence suggests that in the mammalian epidermis, both of these processes occur. During embryonic epidermal development, changes occur in the orientation of the mitotic spindle in relation to the underlying basement membrane. These changes are guided by conserved molecular machinery that is operative in lower eukaryotes and dictates asymmetric partitioning of proteins during cell divisions. That said, the shift in spindle alignment also determines whether a division will be parallel or perpendicular to the basement membrane, and this in turn provides a differential microenvironment for the resulting daughter cells. Here, we review how oriented divisions of progenitors contribute to the development and stratification of the epidermis.

Highlights

  • The interfollicular epidermis of adult mammalian skin is a stratified epithelium, the outermost layer of which is the body surface

  • We review what is known about Asymmetric cell divisions (ACDs) in the developing epidermis, and extrapolate this information to what might be anticipated in adult stem cell niches

  • Much of what we know about the molecular underpinnings of ACDs and spindle orientation comes from Drosophila and Caenorhabditis elegans, where studies in the development of neural progenitors, germline stem cells and zygotes have all been shown to undergo divisions that asymmetrically distribute proteins and organelles into the daughter cells

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Summary

Introduction

The interfollicular epidermis of adult mammalian skin is a stratified epithelium, the outermost layer of which is the body surface (figure 1). In the last stage of terminal differentiation, all metabolic activity ceases, and calcium influx triggers transglutaminase enzymes to cross-link the envelope proteins with indestructible g-glutamyl-1lysine bonds These cells lose their organelles including the nucleus, extrude the lipids on the cornified envelope scaffold and effectively seal the skin surface. In the field of stem cell biology, the term ACD is often more broadly interpreted to include any type of division that yields a differential fate outcome This can happen, for instance, by asymmetric partitioning of proteins during the act of division, and by a symmetric division in which one daughter is either displaced from the stem cell niche and/or otherwise exposed to external differentiation signals relative to the other daughter. We review what is known about ACDs in the developing epidermis, and extrapolate this information to what might be anticipated in adult stem cell niches

Stratification in the epidermis: balancing proliferation and differentiation
Regulation of spindle orientation and asymmetric cell division
Asymmetric versus symmetric divisions: wherein lies the choice?
Inheritance of maternal centrosomes
Notch as an effector for cell fate determination
Conclusions and outstanding questions
Findings
76. Rangarajan A et al 2001 Notch signaling is a direct

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