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Control of neural crest cell fate by the Wnt signalling pathway

Nature volume 396, pages 370–373 (1998)Cite this article

Abstract

Environmental signals are important in the development of neural crest, during which process multipotent progenitor must choose from several fates1,2,3. However, the nature of these environmental signals is unknown. A previous fate map of zebrafish cranial neural crest showed that lineage-restricted clones of pigment cells arise from medial cells near the neural keel, and that clones of neurons arise from lateral cells farther from the neural keel4. Wnt-1 and Wnt-3a are candidate genes for influencing neural crest fate, as they are expressed next to medial, but not lateral, crest cells. Here we determine the role of Wnt signals in modulating the fate of neural crest by injecting messenger RNAs into single, premigratory neural crest cells of zebrafish. Lineage analysis of injected cells shows that activation of Wnt signalling by injection of mRNA encoding cytoplasmic β-catenin promotes pigment-cell formation at the expense of neurons and glia. Conversely, inhibition of the Wnt pathway, by injection of mRNAs encoding either a truncated form of the transcription factor Tcf-3 or a dominant-negative Wnt, promotes neuronal fates at the expense of pigment cells. We conclude that endogenous Wnt signalling normally promotes pigment-cell formation by medial crest cells and thereby contributes to the diversity of neural crest cell fates.

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Figure 1: Analysis of the patterns of expression of Wnt genes in the vicinity of cranial neural crest.
Figure 2: Individual zebrafish neural crest cells injected with GFP mRNA can be traced by GFP expression 24–48 h after injection.
Figure 3: Manipulation of the Wnt pathway affects the fates of neural crest cells.
Figure 4: Model of Wnt function in specification of neural crest cell fate.

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Acknowledgements

We thank G. Kruse for technical support; J. Yang-Snyder for help with related confirmatory experiments (not shown); J. Odenthal for forkhead-6 cDNA; V. Korzh for the Wnt-3a cDNA; and A. Lekven for the Wnt-3a RACE clone. R.I.D. was supported by the Molecular Neurobiology Training Grant from the NIH and R.T.M. acknowledges support as an Investigator of the HHMI. This research was funded by the HHMI (R.T.M.) and the NIH (D.W.R.).

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Authors and Affiliations

  1. Howard Hughes Medical Institute and Department of Pharmacology, Seattle, 98195, Washington, USA

    Richard I. Dorsky & Randall T. Moon

  2. Department of Biological Structure, University of Washington School of Medicine, Seattle, 98195, Washington, USA

    David W. Raible

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  1. Richard I. Dorsky
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  2. Randall T. Moon
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  3. David W. Raible
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Correspondence to Richard I. Dorsky.

Supplementary information

Supplementary Information

Figure legends (DOC 11 kb)

Supplementary Information

Anterior view of uninjected zebrafish embryos stained with a probe for fkd-6 (GIF 91 kb)

Supplementary Information

Anterior view of embryos injected with 1ng of Wnt-1 mRNA, stained for fkd-6. (GIF 84 kb)

Supplementary Information

Dorsal view of injected (top) and Wnt-1-injected (bottom) 48-hour zebrafish embryos. (GIF 87 kb)

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Dorsky, R., Moon, R. & Raible, D. Control of neural crest cell fate by the Wnt signalling pathway. Nature 396, 370–373 (1998). https://doi.org/10.1038/24620

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