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The zebrafish Nodal signal Squint functions as a morphogen

Nature volume 411, pages 607–610 (2001)Cite this article

An Erratum to this article was published on 01 August 2001

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Abstract

Secreted morphogens induce distinct cellular responses in a concentration-dependent manner and act directly at a distance1,2,3,4,5,6,7. The existence of morphogens during mesoderm induction and patterning in vertebrates has been highly controversial, and it remains unknown whether endogenous mesoderm inducers act directly as morphogens8,9,10, function locally9 or act through relay mechanisms11,12. Here we test the morphogen properties of Cyclops and Squint—two Nodal-related transforming growth factor-β signals required for mesoderm formation and patterning in zebrafish13,14,15,16. Whereas different levels of both Squint and Cyclops can induce different downstream genes14,17,18,19, we find that only Squint can function directly at a distance. These results indicate that Squint acts as a secreted morphogen that does not require a relay mechanism.

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Figure 1: Squint has long-range effects, whereas Cyclops has short-range effects.
Figure 2: Squint signals to distant cells either directly or through an Oep-dependent relay signal.
Figure 3: The long-range effect of Sqt does not depend on the induction of the endogenous cyc or sqt genes.
Figure 4: Squint signals directly to distant cells.

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Acknowledgements

We thank members of the Schier and Yelon laboratories for discussions; R. Burdine, A. Carmany-Rampey, K. Joubin, R. Lehmann, G. Struhl, W. Talbot and D. Yelon for comments on the manuscript; S. Zimmerman, R. Feeney and T. Bruno for fish care. Y.C. is the Rebecca Ridley Kry Fellow of the Cancer Research Fund of the Damon Runyon–Walter Winchell Foundation. A.F.S. is a Scholar of the McKnight Endowment Fund for Neuroscience and the Irma T. Hirschl Trust, and is supported by grants from the NIH.

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Authors and Affiliations

  1. Developmental Genetics Program, Skirball Institute of Biomolecular Medicine,

    Yu Chen & Alexander F. Schier

  2. Department of Cell Biology, New York University School of Medicine, New York, 10016, New York, USA

    Yu Chen & Alexander F. Schier

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  1. Yu Chen
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  2. Alexander F. Schier
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Correspondence to Alexander F. Schier.

Supplementary information

Supplementary Fig.1 (JPG 34 KB)

The long-range effect of Sqt is not a result of cell movement. a, illustration of the experiment in b-g; wild-type donor cells labeled with biotin-dextran and rhodamin-dextran (red) are transplanted at a distance from the sqt injected cells (green) at the 1000-2000 cell stage. b-d, b was taken shortly after transplantation; n and o were taken at 1hr (c) and 2hrs (d) after b; the three subsets of the transplanted cells are indicated by arrowheads of different colors. e-g, the embryo in e was fixed immediately after photographing and analyzed by in situ hybridization for ntl expression; red staining marks the transplanted cells produced by detecting the lineage tracer biotin-dextran with the ABC kit from Vectastain; the arrowheads in e-g correspond to those in b-d; three transplanted cells expressing ntl are indicated by the white arrows in g.

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Chen, Y., Schier, A. The zebrafish Nodal signal Squint functions as a morphogen. Nature 411, 607–610 (2001). https://doi.org/10.1038/35079121

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