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Getting under the skin of epidermal morphogenesis

Nature Reviews Genetics volume 3, pages 199–209 (2002)Cite this article

Key Points

  • By combining genetic engineering and cell-biological studies, skin biologists are discovering the mechanisms that underlie the development and differentiation of the epidermis and hair follicles of the skin.

  • Populations of stem cells exist in the basal layer of the epidermis and the hair-follicle bulge. The Notch and Wnt pathways are involved in the decision of the progeny of these cells to commit to an epidermal or hair-follicle fate.

  • Gene-targeting studies of epidermal transcription factor genes have revealed important functional information about the involvement of these factors in balancing differentiation with proliferation and about their role in human genetic skin disorders.

  • Altering the balance between cell proliferation and cell adhesion is required for wound healing and occurs aberrantly in certain skin cancers and skin disorders. New insights into such disorders are being provided by gene targeting and cell-biological studies of the components that make up the main cell junctions of the epidermis.

  • Despite recent insights into the genetic basis of human skin disorders, the therapeutic options for the autosomal-dominant disorders remain bleak. But gene therapy has been successfully used to restore keratinocyte function in certain recessive skin disorders.

  • Recent genetic and cell-biological studies have highlighted the importance of cell adhesion, basement membrane assembly and tissue architecture in contributing to the proper balance and spatial arrangement of epidermal growth and differentiation. But many questions about skin biology remain, which new tools and model systems should help to resolve.

Abstract

At the surface of the skin, the epidermis serves as the armour for the body. Scientists are now closer than ever to understanding how the epidermis accomplishes this extraordinary feat, and is able to survive and replenish itself under the harshest conditions that face any tissue. By combining genetic engineering with cell-biological studies and with human genome data analyses, skin biologists are discovering the mechanisms that underlie the development and differentiation of the epidermis and hair follicles of the skin. This explosion of knowledge paves the way for new discoveries into the genetic bases of human skin disorders and for developing new therapeutics.

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Figure 1: The skin and its appendages.
Figure 2: The Wnt signalling pathway in skin.
Figure 3: Adherens and desmosome junctions in the epidermis.
Figure 4: A hemidesmosome junction.

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Acknowledgements

We thank R. DasGupta, B. J. Merrill and C. Jamora for their critical reading of this review and for their valuable suggestions.

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Authors and Affiliations

  1. Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Room N314, 5841 South Maryland Avenue, Chicago, 60637, Illinois, USA

    Elaine Fuchs & Srikala Raghavan

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  1. Elaine Fuchs
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  2. Srikala Raghavan
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Correspondence to Elaine Fuchs.

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DATABASES

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APC

Apc

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BPAG1e

BPAG2

Catna1

Ccnd1

C/EBP

c-fos

c-Myc

Dkk2

DLK1

Dll1

EGFR

Egfr

ESE2

FGF7

Fgf7

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GM-CSF

hairless

IκB

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IKKγ

IL10

IL20

Itga3

Itgb1

JAG1

JAG2

K19

Klf4

KRT1

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NF-κB

Notch (fly)

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Notch1

p53

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p120ctn

plectin 1

Psen1

Shh

Sp1

STAT3

Stat3

Tcf3

Tgf-α

transferrin receptor

Trp63

VASP

vitamin D receptor 

OMIM 

epidermolysis bullosa simplex

incontinentia pigmenti

junctional epidermolysis bullosa

lamellar ichthyosis

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Mouse Genome Informatics

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FURTHER INFORMATION

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Glossary

MULTIPOTENT STEM CELL

A stem cell that has the potential to give rise to multiple cell lineages.

KERATIN

A cytoskeletal filament that is typically 10 nm in diameter.

SEBOCYTE

A cell of the sebaceous gland.

NEURAL INDUCTION

The specification of cells that give rise to the neural tube and, ultimately, to the central nervous system.

EPIBLAST CELL

A cell in the early embryo that gives rise to all three definitive germ layers of the embryo: the ectoderm, mesoderm and endoderm.

CORNIFIED ENVELOPE

An extremely tough protein lipid polymer structure that forms just below the cytoplasmic membrane of cells of the cornified layer.

E-CADHERIN

A homophilic cell-adhesion molecule that is an important component of the adherens junctions.

ACTIN CYTOSKELETON

A microfilament network that consists of filaments that are 6 nm in diameter and made up of polymerized actin. The actin cytoskeleton forms the main component of the cellular contractile machinery.

INTERMEDIATE FILAMENT CYTOSKELETON

A network that consists of filaments, typically 10 nm in diameter, that contributes to the mechanical strength of cells.

INTEGRIN

A transmembrane protein that functions as a heterodimer and is involved in cell–cell and cell–extracellular-matrix interactions.

REVERSE GENETICS

A genetic analysis that proceeds from genotype to phenotype by gene-manipulation techniques, such as homologous recombination in embryonic stem cells.

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Fuchs, E., Raghavan, S. Getting under the skin of epidermal morphogenesis. Nat Rev Genet 3, 199–209 (2002). https://doi.org/10.1038/nrg758

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