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Patterning the zebrafish axial skeleton requires early chordin function

Nature Genetics volume 23, pages 442–446 (1999)Cite this article

Abstract

Members of the bone morphogenetic protein (BMP) family actively promote ventral cell fates, such as epidermis and blood, in the vertebrate gastrula. More dorsally, the organizer region counteracts BMP signalling through secretion of BMP-binding antagonists chordin and noggin, allowing dorsally derived tissues such as neurectoderm and somitic muscle to develop1. BMPs also function in skeletal development and regeneration of bone following injury2. Noggin antagonism is thought to prevent osteogenesis at sites of joint formation3, whereas chordin has not yet been implicated in skeletogenesis. Analyses of zebrafish mutants have confirmed the action of chordin (chd) in opposing ventralizing signals at gastrulation4,5,6. Some ventralized mutants recover and develop into fertile adults, thereby revealing a requirement for chd function for the later processes of fin and caudal skeletal patterning. We observe in mutants the misexpression of genes encoding BMPs and putative downstream genes, and ectopic sclerotomal cells. Through injections of chd mRNA into the early embryo, we restored wild-type gene expression patterns, and the resultant fish, although genotypically mutant, developed normal axial skeletons and fins. Our results demonstrate that chordin function during gastrulation is important for the correct morphogenesis of the adult zebrafish skeleton.

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Figure 1: Mutant alleles of zebrafish chd.
Figure 2: Fin and skeletal defects of dintt250 homozygous mutants.
Figure 3: Skeletal defects of dintt250 mutants are corrected by mRNA injection.
Figure 4: Gene expression and skeletal abnormalities in ogotm305 mutants.

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Acknowledgements

We thank our colleagues, especially D. Brown and V. Miller-Bertoglio, for useful discussions and critical reading of the manuscript; P. Jagadeeswaran for guidance in radiographic techniques; E. Melancon and J. Eisen for helpful discussions on skeletal development; E. Mountcastle-Shah, W. Driever, E. Egan, W. Talbot, D. Wagner and M. Mullins for sharing information with us before publication; and M. Macurak, A. Hennessy and S.-J. Kim for technical assistance. This work was supported by a Clinical Investigator Development Award from NINDS to S.F. (NS01851-02) and a Pew Scholar Award to M.E.H.

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  1. Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland, USA

    Shannon Fisher & Marnie E. Halpern

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  1. Shannon Fisher
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  2. Marnie E. Halpern
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Correspondence to Shannon Fisher.

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Fisher, S., Halpern, M. Patterning the zebrafish axial skeleton requires early chordin function. Nat Genet 23, 442–446 (1999). https://doi.org/10.1038/70557

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