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Cell intercalation from top to bottom

Nature Reviews Molecular Cell Biology volume 15, pages 34–48 (2014)Cite this article

Subjects

Key Points

  • Cell–cell intercalation is a process that occurs throughout animal development and in which neighbouring cells exchange places. Intercalation can occur within a single plane (for example, mediolateral) or between adjacent planes (radial) and has multiple roles during gastrulation and organogenesis.

  • The Drosophila melanogaster germband and various epithelial tubes in vertebrates (for example, the kidney collecting duct, cochlea and neural tube) undergo epithelial mediolateral intercalation through the contraction and ultimate disassembly of apical junctions that are oriented perpendicular to the axis of tissue extension. When these junctions collapse, rosettes form, which resolve to lengthen the tissue along the axis of extension.

  • Mediolateral intercalation of epithelial cells in some systems involves highly polarized basolateral protrusions that may mediate rearrangement.

  • Mesodermal cells in Xenopus laevis undergo mediolateral intercalation via tractive protrusions and at the same time downregulate C-cadherin-mediated cell–cell adhesions.

  • Some extracellular matrices can act to restrict mesodermal intercalation along a boundary (for example, in the chordate notochord), whereas others serve as a permissive requirement for mesodermal intercalation (for example, fibronectin in amphibian deep cells).

  • Radial intercalation of either deep or epithelial cells depends on contextual cues for successful polarization, protrusion formation and intercalation. Unlike mediolateral intercalation, radial intercalation is generally independent of the planar cell polarity pathway.

Abstract

Animal development requires a carefully orchestrated cascade of cell fate specification events and cellular movements. A surprisingly small number of choreographed cellular behaviours are used repeatedly to shape the animal body plan. Among these, cell intercalation lengthens or spreads a tissue at the expense of narrowing along an orthogonal axis. Key steps in the polarization of both mediolaterally and radially intercalating cells have now been clarified. In these different contexts, intercalation seems to require a distinct combination of mechanisms, including adhesive changes that allow cells to rearrange, cytoskeletal events through which cells exert the forces needed for cell neighbour exchange, and in some cases the regulation of these processes through planar cell polarity.

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Figure 1: Intercalation events drive morphogenesis in diverse contexts during metazoan development.
Figure 2: Intercalation in epithelial cells can be driven through junction remodelling or protrusion formation.
Figure 3: Mediolateral intercalation of deep mesodermal cells in vertebrates.
Figure 4: Radial intercalation drives morphogenesis during gastrulation and later in development.

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Acknowledgements

E.W.-S. was supported by a Genetics Training Grant (US National Institutes of Health (NIH) T32 GM007133). Work in the author's laboratory was supported by NSF grant IOB 0518081 and NIH grant R01 GM58038 (awarded to J.H).

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  1. Graduate Program in Genetics and Department of Zoology, University of Wisconsin-Madison, 250 N Mills Street, Madison, 53706, Wisconsin, USA

    Elise Walck-Shannon & Jeff Hardin

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  1. Elise Walck-Shannon
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Correspondence to Jeff Hardin.

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Glossary

Morphogenesis

The process by which an embryo generates its shape, governed by massive cellular movements.

Gastrulation

The process by which the three primary germ layers (ectoderm, mesoderm and endoderm) are specified and properly positioned.

Mediolateral intercalation

A specific means by which convergent extension can occur in embryos with bilateral symmetry; neighbouring cells within the same plane exchange places with others along the mediolateral axis to elongate the tissue in the orthogonal axis.

Convergent extension

Directional cell rearrangement that results in dramatic lengthening along one axis of a tissue at the expense of narrowing along an orthogonal axis.

Cochlea

The long, coiled region of the inner ear that is required for auditory function.

Radial intercalation

The process by which cells in adjacent layers throughout the thickness of a multilayered tissue exchange places with each another.

Epiboly

The spreading of a tissue, at the expense of its radial thickness, to envelop underlying cells. This process is typically driven by radial intercalation.

Adherens junctions

A protein complex that mediates cell–cell adhesion. It is composed of the transmembrane cell adhesion molecule, cadherin, and catenins, which couple the complex to the actin cytoskeleton. In vertebrate embryos, multiple classes of cadherin exist: E-cadherin is found in epithelia and early mammalian embryos, whereas C-cadherin is found in the early frog embryo during gastrulation.

Germband extension

(GBE). A early phase of Drosophila melanogaster morphogenesis that involves mediolateral intercalation of epidermal cells via shortening of specific cell–cell junctions.

Rosettes

Transient, multicellular structures that are formed as intermediates during epithelial mediolateral intercalation through the collapse of specific cell–cell junctions.

Neural tube closure

A morphogenetic process in vertebrates in which the neuroepithelium intercalates and then folds into a cylinder. Failure of this process leads to common human birth defects.

Notochord

A mesodermal structure that lies below, and aids in the proper specification of, the neural tube. It persists in some chordates but degenerates in most vertebrates.

Chordamesoderm

The axial mesoderm in amphibian embryos, which undergoes extensive convergent extension and eventually gives rise to the notochord. In Xenopus laevis, this tissue is derived from the deep cells of the dorsal involuting marginal zone.

Keller explants

Explants that contain the dorsal marginal zone and that can autonomously undergo convergent extension. They can be microsurgically isolated from part of the Xenopus laevis gastrula.

Prechordal plate

A portion of the involuting marginal zone in Xenopus laevis that ultimately forms the anterior notochord. The prechordal plate mesoderm (PCM) undergoes extensive radial intercalation and involutes before the adjacent chordamesoderm.

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Walck-Shannon, E., Hardin, J. Cell intercalation from top to bottom. Nat Rev Mol Cell Biol 15, 34–48 (2014). https://doi.org/10.1038/nrm3723

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