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  • Review Article
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Mesoderm induction: from caps to chips

Nature Reviews Genetics volume 7, pages 360–372 (2006)Cite this article

Key Points

  • Studies of mesoderm induction in Xenopus and zebrafish trace their origins back to Pieter Nieuwkoop's experiments nearly 40 years ago, and have been a subject of intensive investigation ever since.

  • Four major signalling pathways are involved in this process: Nodal (including Activin and Vg1), FGF (Fibroblast growth factor), canonical Wnt, and BMP (Bone morphogenetic protein), which have both distinct and overlapping roles in the process of mesoderm induction.

  • There are important controversies in the field regarding the existence and function of Nodal gradients in regulating mesoderm formation.

  • The four main signalling pathways interact in different ways to regulate the formation of the head, trunk and tail.

  • The roles of signalling factors in mesoderm induction are seen to change over time, although this is still a relatively new area and further studies will be important.

  • Evidence is emerging for the importance of combinatorial signalling in regulating mesoderm formation.

  • Mesoderm induction is generally conserved among vertebrates, albeit with interesting species-specific differences.

  • New avenues of research will involve defining key mesodermal genes using microarrays and expression screens.

Abstract

Vertebrate mesoderm induction is one of the classical problems in developmental biology. Various developmental biology approaches, particularly in Xenopus and zebrafish, have identified many of the key factors that are involved in this process and have provided major insights into how these factors interact as part of a signalling and transcription-factor network. These data are beginning to be refined by high-throughput approaches such as microarray assays. Future challenges include understanding how the prospective mesodermal cells integrate the various signals they receive and how they resolve this information to regulate their morphogenetic behaviours and cell-fate decisions.

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Figure 1: Fate maps of Xenopus and zebrafish embryos at the late blastula/early gastrula stage.
Figure 2: Models for activation of Nodal signalling in Xenopus and zebrafish.
Figure 3: Establishing the dorsal–ventral axis.
Figure 4: A model for patterning the embryonic body in Xenopus and zebrafish.
Figure 5: Mesoderm induction in the chick and mouse.
Figure 6: Production of different mesodermal cell types from animal cap explants.

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Acknowledgements

I wish to thank A. Schier, E. Amaya, U. Pyati, and D. Szeto for critical comments on this manuscript; C. Stern, H. Isaacs, G. Lieschke, R. Behringer and A. Schier for providing valuable information; and S. Dougan and J. Heasman for communicating unpublished results. D.K.'s work on mesoderm induction is supported by the US National Science Foundation and National Institutes of Health.

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  1. Department of Biochemistry, Box 357350, University of Washington, Seattle, 98195-7350, Washington, USA

    David Kimelman

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FURTHER INFORMATION

Axeldb

Xenopus Mesendoderm Network

ZFIN

Glossary

Blastula

A stage during which the embryo undergoes cleavage to become multicellular. The late blastula stage precedes gastrulation.

Gastrula

A stage during which the embryo undergoes major morphogenetic changes, which positions the endoderm on the inside, the mesoderm in the middle and the ectoderm on the outside.

Organizer

A signalling centre in a vertebrate embryo comprising a group of cells that secrete signalling factors or inhibitors of signalling factors, which changes the fate of the surrounding cells.

Notochord

A rod-shaped structure that runs along the dorsal axis of the embryo, separating the muscle blocks. It is one of the defining features of the phylum Chordata, to which vertebrates belong.

Fate map

A map that shows which tissues are likely to develop from different regions of the embryo.

Morpholinos

Antisense oligonucleotides that are stable and are commonly used in zebrafish and Xenopus to inhibit either the translation or splicing of mRNAs.

Spemann's organizer

A signalling centre in amphibians that is created on the dorsal side of the late blastula embryo. The equivalent centre in fish is called the shield.

Primitive streak

The site of major morphogenetic movements during gastrulation in reptiles, birds and mammals. The mesoderm, as well as the endoderm, moves through this structure as it ingresses.

Epiblast

The portion of the mouse embryo that will become the definitive embryo (as opposed to extra-embryonic tissues).

Amniotes

Include reptiles, birds and mammals, which all have a protective membrane (the amnion) surrounding the embryo that prevents it from desiccating.

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Kimelman, D. Mesoderm induction: from caps to chips. Nat Rev Genet 7, 360–372 (2006). https://doi.org/10.1038/nrg1837

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