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Cadherins in embryonic and neural morphogenesis

Nature Reviews Molecular Cell Biology volume 1, pages 91–100 (2000)Cite this article

Abstract

Cadherins not only maintain the structural integrity of cells and tissues but also control a wide array of cellular behaviours. They are instrumental for cell and tissue polarization, and they regulate cell movements such as cell sorting, cell migration and cell rearrangements. Cadherins may also contribute to neurite outgrowth and pathfinding, and to synaptic specificity and modulation in the central nervous system.

Key Points

  • The cadherin superfamily is one of the main groups of adhesion molecules that mediate cell?cell adhesion in both vertebrates and invertebrates.

  • This diverse superfamily, with over 300 vertebrate members, is defined by the presence of a cadherin domain. A classification of seven subfamilies is presented in this review, on the basis of the domain layout.

  • A predominant function of cadherins is to mediate cell?cell interactions. Structural studies indicate that cadherins form cis dimers in a calcium-dependent manner. Cis dimers are presumably the building blocks for lateral clustering and for trans-dimer formation between cells.

  • Classic cadherins mediate two types of adhesive contacts: diffuse adhesive contacts and ultrastructurally defined cell?cell adherens junctions.

  • Diffuse adhesive contacts are probably formed by oligomerization of cadherin trans dimers. Invertebrate studies indicate that cadherins are not absolutely required for adherens junction formation.

  • Cadherins are also important for forming and maintaining cell polarity in epithelial tissues. Here, they are proposed to mediate localization of the sec 6/8 complex, which in turn directs polarized delivery of molecular components to the membrane.

  • In the fly, cadherins are implicated in mediating planar epithelial polarity. Evidence from both Drosophila and the chick highlight another function for cadherins in generating asymmetric tissue organization, by setting up anterior?posterior and left?right asymmetry, respectively.

  • Cell movements that occur during development require dynamic changes in adhesive interactions. Experiments in Xenopus and Drosophila indicate that cadherins might mediate cell movement during gastrulation and oogenesis, respectively.

  • Cadherins are implicated in central nervous system organization, neurite outgrowth, axon patterning and fasciculation. Later, they are proposed to function in adherens junctions at the synapse. They may be required here to mediate synaptic plasticity, perhaps by providing an adhesive code.

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Figure 1: Structure of the cadherin domain.
Figure 2: Structural diversity of the cadherin superfamily.
Figure 3: Ca2+-mediated cis- and trans-dimer formation of vertebrate classic cadherins.
Figure 4: Comparison between cadherin-mediated adhesive interactions at epithelial and synaptic adherens junctions.
Figure 5: Cadherins in apicobasal and planar epithelial polarity.
Figure 6: Cell movements that involve cadherins.

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Acknowledgements

We would like to thank Y. Takai, J. Petite, R. Cagan and T. Uemura for communicating unpublished results. The work on cadherins in the authors' laboratories is funded by grants from the National Cancer Institute of Canada with funds from the Canadian Cancer Society (to U.T. and M.I.), the Canadian Institute for Health Research (to U.T. and D.G.), University of Toronto Connaught Committee (to D.G.), the National Institutes of Health (to M.P.), the Human Frontier Science Program (to M.P.) and the US Army Breast Cancer Research Program (to M.P.).

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Authors and Affiliations

  1. Department of Zoology, University of Toronto, 25 Harbord Street, Toronto, M5S 3G5, Ontario, Canada

    Ulrich Tepass & Dorothea Godt

  2. Division of Molecular and Structural Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, M5G 2M9, Ontario, Canada

    Kevin Truong & Mitsuhiko Ikura

  3. Department of Biology, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Mark Peifer

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  1. Ulrich Tepass
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Corresponding author

Correspondence to Ulrich Tepass.

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FURTHER INFORMATION

The cadherin resource

Cadherin web site at the LMB, Cambridge

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ENCYCLOPEDIA OF LIFE SCIENCES

Adhesive specificity and the evolution of multicellularity

Glossary

GROWTH CONE

Exploratory tip of an extending neuronal process such as an axon.

IMMUNOGLOBULIN-TYPE ADHESION MOLECULES

Family of adhesion molecules characterized by the presence of immunoglobulin-like domains, which are also found in antibody molecules.

CHORDATES

Phylum that comprises animals with a notochord and includes all vertebrates.

DESMOSOME

A patch-like adhesive intercellular junction found in vertebrate tissues that is linked to intermediate filaments.

METAZOANS

Refers to the kingdom Animalia (animals) that comprises roughly 35 phyla of multicellular organisms.

ADHERENS JUNCTIONS

Cell?cell or cell?matrix adhesive junctions that are linked to microfilaments.

ECHINODERMS

Animal phylum of marine invertebrates including sea urchins and starfish.

ARTHROPODS

Largest animal phylum composed of invertebrates that have a segmented body, segmented appendages and an external skeleton. This includes insects, spiders and crustaceans.

NEMATODES

Animal phylum of unsegmented roundworms.

GENE RADIATION

Process that leads to the formation of gene families in which gene amplification through gene duplication events is followed by the diversification of gene structure and function.

ZONULA ADHERENS

A cell?cell adherens junction that forms a circumferential belt around the apical pole of epithelial cells.

PDZ DOMAINS

Protein?protein interaction domain, first found in PSD-95, DLG and ZO-1.

SH3 DOMAINS

Src homology region 3 domains. Protein sequences of about 50 amino acids that recognize and bind sequences rich in proline.

FILOPODIUM

Finger-like exploratory cell extension found in crawling cells and growth cones.

LAMELLIPODIUM

Thin sheet-like cell extension found at the leading edge of crawling cells or growth cones

FOLLICLE CELLS

In this review, the term follicle cells refers to cells that surround the developing insect egg and secrete the egg membranes, the chorion and vitelline envelope.

GASTRULATION

Series of morphogenetic movements observed during the early development of most animals that leads to the formation of a multilayered embryo with an outer cell layer (ectoderm), an inner cell layer (endoderm), and an intermediate cell layer (mesoderm).

NEUROEPITHELIUM

Epithelial layer of cells that gives rise to the nervous system.

NEURULATION

Morphogenetic process during which the progenitors of the nervous system segregate from the ectoderm.

NEURITE

Process extended by a nerve cell that can give rise to an axon or a dendrite.

FASCICULATION

Bundling of axonal processes of neurons.

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Tepass, U., Truong, K., Godt, D. et al. Cadherins in embryonic and neural morphogenesis. Nat Rev Mol Cell Biol 1, 91–100 (2000). https://doi.org/10.1038/35040042

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