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Boundary formation and maintenance in tissue development

Nature Reviews Genetics volume 12, pages 43–55 (2011)Cite this article

Subjects

Key Points

  • Straight and sharp boundaries often separate groups of cells with distinct functions or fates during animal development. The formation and maintenance of such boundaries is important for the growth and patterning of tissues.

  • Straight and sharp boundaries are challenged by cell rearrangements caused by cell proliferation or tissue deformation.

  • Two basic types of boundaries can be defined: non-lineage boundaries, in which cell identity is plastic and cells can move across gene expression boundaries and adapt their identity to their local neighbours; and lineage (or compartment) boundaries in which cell identity is inherited and straight and sharp boundaries between groups of cells with distinct identities are maintained by cell sorting.

  • Boundaries between the somites of vertebrate embryos are examples of non-lineage boundaries. Mesoderm posterior (Mesp) transcription factors are key players in the pre-patterning that defines the position and identity of somites.

  • Boundaries within the vertebrate hindbrain and the developing Drosophila melanogaster wing are examples of compartment boundaries. Selector genes provide cell identity to compartments in D. melanogaster.

  • Cell signalling is important for maintaining boundaries. Ephrin receptor (Eph)–ephrin signalling is required to maintain compartment boundaries in the vertebrate hindbrain and the non-lineage boundaries between the somites.

  • The deposition of extracellular matrix is a key physical mechanism to maintain somite boundaries.

  • Differential mechanical tension has emerged as a new principle to maintain compartment boundaries in D. melanogaster tissues.

Abstract

The formation and maintenance of boundaries between neighbouring groups of embryonic cells is vital for development because groups of cells with distinct functions must often be kept physically separated. Furthermore, because cells at the boundary often take on important signalling functions by acting as organizing centres, boundary shape and integrity can also control the outcome of many downstream patterning events. Recent experimental findings and theoretical descriptions have shed new light on classic questions about boundaries. In particular, in the past couple of years the role of forces acting in epithelial tissues to maintain boundaries has emerged as a new principle in understanding how early pattern is made into permanent anatomy.

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Figure 1: Boundary concepts: challenges and mechanisms.
Figure 2: Developmental boundaries in the developing fruitfly and vertebrate embryo.
Figure 3: Formation and maintenance of the somite boundary.
Figure 4: Mechanical tension in embryonic and larval Drosophila melanogaster epithelia.

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Acknowledgements

The authors would like to thank Y. Saga, Y. Takahashi and S. Holley for comments on the manuscript. We thank D. Umetsu for help in preparing Figure 2. We apologize to all authors whose primary work we could not cite owing to space limitations. Work in the laboratory of C.D. is supported by the Max Planck Society, the Deutsche Forschungsgemeinschaft and the Human Frontiers Science Program. A.C.O. is supported by the Max Planck Society and the European Research Council under the European Communities Seventh Framework Programme (FP7/2007-2013) / ERC grant no. 207634. M.B. is supported by the TU Dresden, the Deutsche Forschungsgemeinschaft (SFB 655 and CRTD) and the European Union (ZF Health).

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Authors and Affiliations

  1. Biotechnology Center, BIOTEC and Center for Regenerative Therapies (CRTD), Dresden University of Technology, Tatzberg 47/49, 01307, Dresden, Germany

    Christian Dahmann & Michael Brand

  2. Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Pfotenhauerstrasse 108, 01307, Dresden, Germany

    Christian Dahmann & Andrew C. Oates

  3. Institute of Genetics, Dresden University of Technology, Zellescher Weg 20b, 01217, Dresden, Germany

    Christian Dahmann

  4. Christian Dahmann

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Glossary

French flag model

A tissue-patterning scenario in which a gradient of secreted signal causes a concentration-dependent activation of three target genes in non-overlapping and abutting domains across a field of initially undifferentiated cells. The idea comes from Lewis Wolpert, and the name refers to the three fields of colour on the French flag.

Paraxial mesoderm

The bilaterally symmetrical tissue extending from the tail to the head of the vertebrate embryo that forms somites and their derivatives, such as bone, muscle, tendons and skin.

Mesenchymal-to-epithelial transition

The process whereby a mesenchymal population of cells rearrange their local positions and cell polarity to build an epithelium.

Telencephalon

The most anterior segment of the vertebrate brain. It gives rise to the forebrain and, in mammals, the neocortex.

Zona limitans intrathalamica

A zone that divides the dorsal and ventral thalamus of the forebrain.

Wing imaginal disc

An epithelial tissue that gives rise to the wings and parts of the body wall of adult flies. It is subdivided by the anteroposterior and dorsoventral compartment boundaries.

Tension

A force relating to the stretching of an object; the opposite of compression.

Hox gene family

A family of homeobox DNA-binding domain-containing transcription factors that were initially identified by their function in homeotic transformations.

Rhombomere

The basic unit of segmental organization in the hindbrain. The rhombomere has lineage or compartment boundaries.

Basic helix–loop–helix

A family of transcription factors that are characterized by their basic helix–loop–helix DNA binding and dimerization domain structure.

Clock and wavefront

A mechanism for segmentally patterning the vertebrate paraxial mesoderm, involving a cellular oscillator, the clock, in the cells of the presomitic mesoderm, and a wavefront of differentiation that arrests the clock as it moves across the presomitic mesoderm.

Integrin

A cell surface transmembrane protein that binds fibronectin; integrins are usually associated with focal adhesion complexes.

Fibronectin

An extracellular matrix glycoprotein that is capable of forming fibrils, a ligand for integrins.

Ephrin reverse signalling

The activity of ephrin cell surface proteins, initially thought to be ligands only, to transduce a signal from the Eph-type receptor tyrosine kinase.

Cadherin

A cell surface transmembrane calcium-dependent cell-adhesion protein that is capable of homophilic binding. Cadherins are usually associated with adherens junctions in epithelial tissue.

Chromophore-assisted laser inactivation

The use of high-intensity laser light delivered to subcellular locations with fluorescently tagged proteins of interest to inactivate them through the local release of free radicals from the stimulated chromophore.

Adherens junctions

Multiprotein membrane complexes that mediate adhesion between epithelial cells. Adherens junctions contain cadherins, α- and β-catenins, and p120, the cytoplasmic faces of which connect to the actin cytoskeleton.

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Dahmann, C., Oates, A. & Brand, M. Boundary formation and maintenance in tissue development. Nat Rev Genet 12, 43–55 (2011). https://doi.org/10.1038/nrg2902

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