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Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis

Nature Reviews Molecular Cell Biology volume 12, pages 565–580 (2011)Cite this article

Subjects

Key Points

  • The epidermis is a specialized multilayered epithelium that provides a protective environmental barrier while also undergoing dynamic turnover and responding rapidly to injury.

  • Keratinocytes of the epidermis undergo several transformations as they differentiate and migrate outwards to replace cells that are shed at the body surface, thus maintaining epidermal homeostasis. Dynamic changes in adhesive junctions and the cytoskeleton of keratinocytes are a driving force in this morphogenesis.

  • In the basal layers, keratinocytes are tightly adhered to the basement membrane through integrin-based adhesions and hemidesmosomes and continue to proliferate through crosstalk between integrins and growth factor receptors. During stratification, orientated asymmetric cell divisions allow keratinocytes to move upwards into the spinous layer.

  • Keratinocytes in the spinous layer exit the cell cycle and establish increased intercellular connections, such as through desmosomes. They also induce signalling changes to promote epidermal differentiation and form tight junctions that provide an epidermal barrier. Components of the cytoskeleton, including the microtubule network, also dynamically rearrange in differentiating keratinocytes.

  • In the upper epidermis, keratinocytes generate a cornified envelope and unique junctions termed corneodesmosomes, which are assembled during the final stages of differentiation and cleaved to allow desquamation.

  • Several cytoskeletal and adhesive components are implicated in human diseases of the epidermis, highlighting the important role that these structural components have in actively ensuring normal epidermal homeostasis.

Abstract

To provide a stable environmental barrier, the epidermis requires an integrated network of cytoskeletal elements and cellular junctions. Nevertheless, the epidermis ranks among the body's most dynamic tissues, continually regenerating itself and responding to cutaneous insults. As keratinocytes journey from the basal compartment towards the cornified layers, they completely reorganize their adhesive junctions and cytoskeleton. These architectural components are more than just rivets and scaffolds — they are active participants in epidermal morphogenesis that regulate epidermal polarization, signalling and barrier formation.

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Figure 1: Epidermal architecture.
Figure 2: Integrins crosstalk with growth factor receptors to regulate proliferation in the basal layer.
Figure 3: Mitotic spindle orientation directs stratification.
Figure 4: Desmoplakin regulates microtubule reorganization in the stratified epidermis.
Figure 5: Tight junction dynamics during antigen sampling.

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Acknowledgements

The authors would like to thank M. Amagai, J. Jones, T. Lechler and T. Magin for critical reading of the manuscript and/or advice on figures. We also apologize to our colleagues whose work we were unable to include owing to space limitations. The authors are supported by US National Institutes of Health grants AR043380, AR041836 and CA122151, the Leducq Foundation and the J.L. Mayberry Endowment to K.J.G.

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Authors and Affiliations

  1. Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, 60611, Illinois, USA

    Cory L. Simpson, Dipal M. Patel & Kathleen J. Green

  2. Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, 60611, Illinois, USA

    Kathleen J. Green

  3. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, 60611, Illinois, USA

    Kathleen J. Green

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Glossary

Organotypic

An in vitro reconstituted model of a tissue grown from cultured cellular elements.

Filopodia

Thin, transient actin protrusions that extend out from the cell surface and are formed by the elongation of bundled actin filaments in their cores.

Endocytic sites

Sites of endocytosis, which is the internalization and transport of extracellular material and plasma membrane proteins from the cell surface to intracellular organelles known as endosomes.

Transglutaminases

(TGases). A family of enzymes that can catalyse covalent bond formation between a glutamine on a peptide and a free amine group.

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Simpson, C., Patel, D. & Green, K. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol 12, 565–580 (2011). https://doi.org/10.1038/nrm3175

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