Complex networks orchestrate epithelial–mesenchymal transitions

Key Points

  • Epithelial and mesenchymal cells have distinct characteristics. These cell types can be partially or fully interconverted through the processes of epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition (MET).

  • EMT is controlled by various extracellular triggers. The intracellular pathways that are activated by these triggers exhibit extensive crosstalk and have many common endpoints.

  • Biophysics as well as cell- and molecular-biology approaches have been combined to provide many novel insights into the process of EMT.

  • EMT has an important role in many embryological processes. Examples include gastrulation, neural-crest development and heart-valve formation.

  • There is mounting evidence that EMT processes are involved in several pathological processes, including would healing, fibrosis and cancer.

  • Better model systems and the identification of genes that mark specific EMT events are required for further progress in this field.

Abstract

Epithelial–mesenchymal transition is an indispensable mechanism during morphogenesis, as without mesenchymal cells, tissues and organs will never be formed. However, epithelial-cell plasticity, coupled to the transient or permanent formation of mesenchyme, goes far beyond the problem of cell-lineage segregation. Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.

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Figure 1: Images of EMT.
Figure 2: The cycle of epithelial-cell plasticity.
Figure 3: Overview of the molecular networks that regulate EMT.
Figure 4: Molecular events in junctional complexes during EMT.
Figure 5: Tissue remodelling and EMT.
Figure 6: Different signalling pathways cooperate to regulate EMT during neural-crest determination and segregation.

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Acknowledgements

This work was supported, in part, by the European Union under the auspices of the European Economic Comunity Framework Programme 6 Specific Targeted Research Project BRECOSM (Breast Cancer Metastasis). This review is dedicated to the memory of Professor Shoichiro Tsukita of Kyoto University who passed away in December 2005.

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Glossary

Mesoderm

In animals with three tissue layers, the mesoderm is the middle layer of tissue, lying between the ectoderm and the endoderm. In vertebrates, it forms the skeleton, muscles, heart, spleen, kidney and other internal organs.

Endoderm

The innermost germ layer of the developing embryo. It gives rise to the lungs, digestive tract, thyroid, thymus, liver and pancreas.

Phyla

Large groups of species that share the same body plan. The animal kingdom is composed of about 30 phyla including Porifera, Cnidaria, Arthropoda, Echinodermata, and Chordata, which includes the Vertebrata as a subphylum.

Porifera

The most primitive phylum of the animal kingdom, it includes sponges.

Cnidaria

Radially symmetrical animals that form a phylum that includes jellyfish, corals, hydra and anemonies.

Blastula stage

An early-stage embryo that is composed of a hollow ball of cells.

Primitive colonial protozoans

Single-celled organisms that live in colonies — they might be the organisms from which Porifera developed.

Diploblastic

Animals that are composed of two cell layers. They belong to the phylum Cnidaria.

Ectoderm

The outermost of the three primary germ layers of the embryo, from which the skin, nerve tissue and sensory organs develop.

Mesenchyme

Embryonic tissue that is composed of loosely organized, unpolarized cells of both mesodermal and ectodermal (for example, neural crest) origin, with a component-rich extracellular matrix.

Organizer

A small dorsal region of the vertebrate gastrula-stage embryo that has the remarkable capacity to organize a complete embryonic body plan. Hilde Mangold and Hans Spemann first identified the organizer in amphibian embryos using tissue transplantation.

Mesendoderm

Cells that form early during gastrulation in the vertebrate and are destined to give rise to mesodermal and endodermal derivatives.

Rostrocaudal

The anterior–posterior (head to tail) polarity of animals.

Neural crest

A transient embryonic structure of vertebrates that appears in the ectoderm at the junction between the neural plate and lateral ectoderm. This structure gives rise to many distinct derivatives following precise migratory routes at each axial level. The derivatives include cranio–facial structures (cartilage, bone, muscles), melanocytes, adrenal medulla, and cells of the sensory and autonomic nervous systems.

Basement membrane

An extracellular-matrix structure that can be visualized by light microscopy and lines the basal side of epithelia.

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Thiery, J., Sleeman, J. Complex networks orchestrate epithelial–mesenchymal transitions. Nat Rev Mol Cell Biol 7, 131–142 (2006). https://doi.org/10.1038/nrm1835

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