DOI: 10.1101/gad.10.19.2452. Genetic analysis of dorsoventral pattern formation in the zebrafish: requirement of a BMP-like ventralizing activity and its dorsal repressor.

Genetic analysis of dorsoventral pattern formation in the zebrafish: requirement of a BMP-like ventralizing activity and its dorsal repressor.

10.1101/gad.10.19.2452

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

According to a model based on embryological studies in amphibia, dorsoventral patterning is regulated by the antagonizing function of ventralizing bone morphogenetic proteins (BMPs) and dorsalizing signals generated by Spemann's organizer. Large-scale mutant screens in the zebrafish, Danio rerio, have led to the isolation of two classes of recessive lethal mutations affecting early dorsoventral pattern formation. dino mutant embryos are ventralized, whereas swirl mutants are dorsalized. We show that at early gastrula stages, dino and swirl mutants display an expanded or reduced Bmp4 expression, respectively. The dino and swirl mutant phenotypes both can be phenocopied and rescued by the modulation of BMP signaling in wild-type and mutant embryos. By suppressing BMP signaling in dino mutants, adult fertile dino -/- fish were generated. These findings, together with results from the analysis of dino-swirl double mutants, indicate that dino fulfills its dorsalizing activity via a suppression of swirl-dependent, BMP-like ventralizing activities. Finally, cell transplantation experiments show that dino is required on the dorsal side of early gastrula embryos and acts in a non-cell-autonomous fashion. Together, these results provide genetic evidence in support of a mechanism of early dorsoventral patterning that is conserved among vertebrate and invertebrate embryos.

Bibliography

Hammerschmidt, M., Serbedzija, G. N., & McMahon, A. P. (1996). Genetic analysis of dorsoventral pattern formation in the zebrafish: requirement of a BMP-like ventralizing activity and its dorsal repressor. Genes & Development, 10(19), 2452â2461.

Authors 3

M Hammerschmidt (first)
G N Serbedzija (additional)
A P McMahon (additional)

References 47 Referenced 180

10.1242/dev.115.2.573 / Development / Bone morphogenetic protein 4: A ventralizing factor in early Xenopus development. (1992)
10.1038/380027a0
10.1073/pnas.92.23.10713
10.1002/j.1460-2075.1994.tb06830.x / EMBO J. / On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo. (1994)
10.1016/0092-8674(92)90514-D
10.1242/dev.114.3.583 / Development / Localized enhancement or repression of the activity of the TGF-β family member, decapentaplegic, is necessary for dorsal-ventral pattern formation in the Drosophila embryo. (1992)
10.1016/0092-8674(95)90446-8
10.1101/gad.8.21.2602
10.1016/0092-8674(94)90409-X
10.1242/dev.123.1.1 / Development / The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. (1996)
10.1101/gad.10.6.647
10.1242/dev.123.1.95 / Development / dino and mercedes, two genes regulating dorsal development in the zebrafish embryo. (1996)
10.1101/gad.9.23.2923
10.1016/0092-8674(94)90320-4
{'key': '2021111418401076000_10.19.2452.15', 'first-page': '53', 'article-title': 'Axis formation in the embryo of the zebrafish, Brachydanio rerio.', 'volume': '3', 'year': '1992', 'journal-title': 'Sem. Dev. Biol.'} / Sem. Dev. Biol. / Axis formation in the embryo of the zebrafish, Brachydanio rerio. (1992)
10.1038/348728a0
10.1038/376249a0
10.1242/dev.119.4.1261 / Development / The ventral and posterior expression of the homeobox gene eve1 is perturbed in dorsalized and mutant embryos. (1993)
10.1016/S0960-9822(95)00112-6
10.1242/dev.115.2.639 / Development / DVR-4 (bone morphogenetic protein-4) as a posterior ventralizing factor in Xenopus mesoderm induction. (1992)
10.1242/dev.122.5.1545 / Development / Bone morphogenetic protein-4 (BMP-4) acts during gastrula stages to cause ventralization of Xenopus embryos. (1996)
10.1073/pnas.91.22.10260
10.1101/gad.9.24.3027
10.1242/dev.123.1.81 / Development / Genes establishing dorsal-ventral pattern formation in the zebrafish embryo: The ventral specifying genes. (1996)
{'key': '2021111418401076000_10.19.2452.25', 'first-page': '836', 'article-title': 'Activin-binding protein from rat ovary is Follistatin.', 'volume': '247', 'year': '1989', 'journal-title': 'Science'} / Science / Activin-binding protein from rat ovary is Follistatin. (1989)
10.1038/325081a0
10.1242/dev.110.4.1041 / Development / A Drosophila growth factor homolog, decapentaglegic regulates homeotic gene expression within and across germ layers during midgut morphogenesis. (1990)
10.1016/S0092-8674(00)80132-4
10.1242/dev.110.4.1031 / Development / Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos. (1990)
10.1016/0092-8674(94)90068-X
10.1038/376333a0
10.1242/dev.121.12.4319 / Development / Drosophila short gastrulation induces an ectopic axis in Xenopus: Evidence for conserved mechanisms of dorsal-ventral patterning. (1995)
10.1006/dbio.1995.1124
10.1242/dev.116.4.1021 / Development / The protein product of the zebrafish homologue of the mouse T gene is expressed in nuclei of the germ ring and the notochord of the early embryo. (1992)
10.1242/dev.120.4.843 / Development / Expression of the zebrafish goosecoid and no tail gene products in wild-type and mutant ntl embryo. (1994)
10.1242/dev.122.4.1313 / Development / Characterization of the zebrafish organizer: Microsurgical analysis at the early-shield stage. (1996)
10.1101/gad.7.1.1 / Genes & Dev. / The frog prince-ss: A molecular formula for dorsoventral patterning in Xenopus. (1993)
10.1016/0092-8674(92)90316-5
10.1242/dev.117.4.1261 / Development / Lithium perturbation and goosecoid expression identify a dorsal pecification pathway in the pregastrula zebrafish. (1993)
10.1002/j.1460-2075.1995.tb00208.x / EMBO J. / The role of gsc and BMP-4 in dorsal-ventral patterning of the marginal zone in Xenopus: A loss-of-function study using antisense RNA. (1995)
10.1101/gad.7.7b.1436
10.1073/pnas.91.22.10255
10.1006/dbio.1994.1212
10.1242/dev.117.2.807 / Development / An activity gradient of decapentaplegic is necessary for the specification of dorsal pattern elements in the Drosophila embryo. (1993)
10.1038/376331a0
10.1101/gad.9.17.2105
10.1016/S0092-8674(00)80133-6

Dates

Type	When
Created	18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 9:55 p.m.)
Indexed	1 month, 1 week ago (July 24, 2025, 8:14 a.m.)
Issued	28 years, 11 months ago (Oct. 1, 1996)
Published	28 years, 11 months ago (Oct. 1, 1996)
Published Online	28 years, 11 months ago (Oct. 1, 1996)
Published Print	28 years, 11 months ago (Oct. 1, 1996)

Funders 0

None

BibTeX

@article{Hammerschmidt_1996, title={Genetic analysis of dorsoventral pattern formation in the zebrafish: requirement of a BMP-like ventralizing activity and its dorsal repressor.}, volume={10}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.10.19.2452}, DOI={10.1101/gad.10.19.2452}, number={19}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Hammerschmidt, M and Serbedzija, G N and McMahon, A P}, year={1996}, month=oct, pages={2452–2461} }

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      "URL": "http://genesdev.cshlp.org/lookup/doi/10.1101/gad.10.19.2452"
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  "subtitle": [],
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  "issued": {
    "date-parts": [
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        1
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  "journal-issue": {
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  "ISSN": [
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  "subject": [],
  "container-title-short": "Genes Dev.",
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        10,
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}