Crossref journal-article
The Company of Biologists
Development (237)
Abstract

ABSTRACT Injection of RNA encoding BMP-4 into the early Xenopus embryo suppresses formation of dorsal and anterior cell types. To understand this phenomenon, it is necessary to know the stage at which BMP-4 acts. In this paper, we present three lines of evidence showing that BMP-4 misexpression has no effect on the initial steps of mesoderm induction, either dorsal or ventral, but instead causes ventralization during gastrulation. Firstly, activation of organizer-specific genes such as goosecoid, Xnot, pintallavis and noggin occurs normally in embryos injected with BMP-4 RNA, but transcript levels are then rapidly downregulated as gastrulation proceeds. Similarly, BMP-4 does not affect the initial activation of goosecoid by activin in animal caps, but expression then declines precipitously. Secondly, embryos made ventral by injection with BMP-4 RNA cannot be rescued by grafts of Spemann’s organizer at gastrula stages. Such embryos therefore differ from those made ventral by UV-irradiation, where the defect occurs early and rescue can be effected by the organizer. Finally, the dorsalizing effects of the organizer, and of the candidate dorsalizing signal noggin, both of which exert their effects during gastrulation, can be counteracted by BMP-4. Together, these experiments demonstrate that BMP-4 can act during gastrulation both to promote ventral mesoderm differentiation and to attenuate dorsalizing signals derived from the organizer.

Authors 5
  1. C. Michael Jones (first)
  2. Leslie Dale (additional)
  3. Brigid L. M. Hogan (additional)
  4. Christopher V. E. Wright (additional)
  5. J. C. Smith (additional)
References 60 Referenced 125
  1. 10.1126/science.1677215 / Science / Organizer-specific homeobox genes in Xenopus laevis embryos by Blumberg (1991)
  2. 10.1007/BF00575837 / Wilhelm Roux Arch. EntwMech. Org / The formation of the mesoderm in urodelean amphibians. V. Its regional induction by the endoderm by Boterenbrood (1973)
  3. 10.1101/gad.4.11.1910 / Genes Dev / Differential activation of Xenopus homeobox genes by mesoderm-inducing growth factors and retinoic acid by Cho (1990)
  4. 10.1016/0092-8674(91)90288-A / Cell / Molecular nature of Spemann’s organizer: the role of the Xenopus homeobox gene goosecoid by Cho (1991)
  5. 10.1101/gad.7.1.13 / Genes Dev / Interactions between Xwnt-8 and Spemann organizer signalling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus by Christian (1993)
  6. {'key': '2025021322490844800_DEVELOP_122_5_1545C6', 'first-page': '3376', 'article-title': 'Most of the homeobox-containing Xhox 36 transcripts in early Xenopus embryos cannot encode a homeodomain protein', 'volume': '10', 'author': 'Condie', 'year': '1990', 'journal-title': 'Mol. Cell Biol'} / Mol. Cell Biol / Most of the homeobox-containing Xhox 36 transcripts in early Xenopus embryos cannot encode a homeodomain protein by Condie (1990)
  7. 10.1242/dev.99.4.527 / Development / Fate map for the 32-cell stage of Xenopus laevis by Dale (1987)
  8. 10.1242/dev.100.2.279 / Development / Regional specification within the mesoderm of early embryos of Xenopus laevis by Dale (1987)
  9. {'key': '2025021322490844800_DEVELOP_122_5_1545C9', 'first-page': '289', 'article-title': 'Mesoderm induction in Xenopus laevis: a quantitative study using a cell lineage label and tissue specific antibodies', 'volume': '89', 'author': 'Dale', 'year': '1985', 'journal-title': 'J. Embryol. Exp. Morph'} / J. Embryol. Exp. Morph / Mesoderm induction in Xenopus laevis: a quantitative study using a cell lineage label and tissue specific antibodies by Dale (1985)
  10. 10.1242/dev.115.2.573 / Development / Bone morphogenetic protein 4: A ventralising factor in early Xenopus development by Dale (1992)
  11. 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 by Fainsod (1994)
  12. 10.1016/0092-8674(92)90514-D / Cell / decapentaplegic acts as a morphogen to organise dorso-ventral pattern in the Drosophila embryo by Ferguson (1992)
  13. 10.1016/0092-8674(95)90446-8 / Cell / Xenopus chordin and Drosophila short gastrulation genes encode homologous proteins functioning in dorsal-ventral axis formation by François (1995)
  14. 10.1101/gad.8.21.2602 / Genes Dev / Dorso-ventral patterning of the Drosophila embryo depends on a putative negative growth factor encoded by the short gastrulation gene by François (1994)
  15. 10.1016/0012-1606(84)90042-3 / Dev. Biol / Early cellular interactions promote embryonic axis formation in Xenopus laevis by Gimlich (1984)
  16. 10.1016/0092-8674(94)90409-X / Cell / Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo by Graff (1994)
  17. 10.1016/0092-8674(94)90320-4 / Cell / Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity by Hemmati-Brivanlou (1994)
  18. 10.1002/dvg.1020170109 / Dev. Genet / Ventral mesodermal patterning in Xenopus embryos: Expression patterns and activities of BMP-2 and BMP-4 by Hemmati-Brivanlou (1995)
  19. 10.1038/376249a0 / Nature / A conserved system for dorso-ventral patterning in insects and vertebrates involving sog and chordin by Holley (1995)
  20. 10.1242/dev.1994.Supplement.53 / Development / Growth factors in development: the role of TGF-ß related polypeptide signalling molecules in embryogenesis by Hogan (1994)
  21. 10.1006/bbrc.1995.2587 / Biochem. Biophys. Res. Comm / Truncated type II receptor for BMP-4 induces secondary axial structures in Xenopus embryos by Ishikawa (1995)
  22. 10.1242/dev.115.2.639 / Development / DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction by Jones (1992)
  23. 10.1016/S0960-9822(95)00112-6 / Current Biol / Revolving vertebrates by Jones (1995)
  24. 10.1242/dev.121.11.3651 / Development / Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation by Jones (1995)
  25. 10.1016/0012-1606(88)90189-3 / Dev. Biol / The entire mesodermal mantle behaves as Spemann’s organizer in dorso-anterior enhanced Xenopus laevis embryos by Kao (1988)
  26. 10.1242/dev.121.7.2155 / Development / Induction of dorsal mesoderm by soluble, mature Vg1 protein by Kessler (1995)
  27. 10.1038/308067a0 / Nature / Monoclonal antibodies identify blastema cells derived from differentiating muscle in newt limb regeneration by Kintner (1984)
  28. 10.1016/0925-4773(91)90027-4 / Mech. Dev / Bone morphogenetic protein 4 (BMP-4) a member of the TGF-β family in early embryos of Xenopus laevis: analysis of mesoderm inducing activity by Köster (1991)
  29. 10.1016/0012-1606(89)90300-X / Dev. Biol / The mRNA encoding elongation factor 1-alpha (EF-1 alpha) is a major transcript at the midblastula transition in Xenopus by Krieg (1989)
  30. 10.1242/dev.117.1.263 / Development / Properties of the dorsalizing signal in gastrulae of Xenopus laevis by Lettice (1993)
  31. 10.1073/pnas.91.22.10260 / Proc. Natl. Acad. Sci. USA / A truncated bone morphogenetic protein 4 receptor alters the fate of ventral mesoderm to dorsal mesoderm: roles of animal pole tissue in the development of ventral mesoderm by Maeno (1994)
  32. 10.1038/311716a0 / Nature / Cell type specific activation of actin genes in the early amphibian embryo by Mohun (1984)
  33. 10.1016/0012-1606(87)90296-X / Dev. Biol / Fates of the blastomeres of the 32 cell Xenopus embryo by Moody (1987)
  34. {'volume-title': 'Normal Table of Xenopus laevis (Daudin)', 'year': '1967', 'author': 'Nieuwkoop', 'key': '2025021322490844800_DEVELOP_122_5_1545C34'} / Normal Table of Xenopus laevis (Daudin) by Nieuwkoop (1967)
  35. 10.1016/S0006-291X(05)81574-8 / Biochem. Biophys. Res. Comm / Genes for bone morphogenetic proteins are differentially transcribed in early amphibian embryos by Nishimatsu (1992)
  36. 10.1242/dev.121.5.1351 / Development / Patterning of the mesoderm in Xenopus: dose-dependent and synergistic effects of Brachyury and Pintallavis by O’Reilly (1995)
  37. 10.1073/pnas.92.26.12141 / Proc. Natn. Acad. Sci. USA / Competition between noggin and bone morphogenetic protein 4 activities may regulate dorsalization during Xenopusdevelopment by Re’em-Kalma (1995)
  38. 10.1242/dev.116.1.81 / Development / Pintallavis, a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis by Ruiz I Altaba (1992)
  39. 10.1242/dev.106.1.173 / Development / Bimodal and graded expression of the Xenopus homeobox gene Xhox3 by Ruiz I Altaba (1989)
  40. 10.1016/0092-8674(94)90068-X / Cell / Xenopus chordin: A novel dorsalizing factor activated by organizer-specific homeobox genes by Sasai (1994)
  41. 10.1038/376333a0 / Nature / Regulation of neural induction by the Chd and BMP-4 antagonistic patterning signals in Xenopus by Sasai (1995)
  42. 10.1242/dev.109.4.967 / Development / Identification in Xenopus of a structural homologue of the Drosophila gene snail by Sargent (1990)
  43. {'key': '2025021322490844800_DEVELOP_122_5_1545C43', 'first-page': '37', 'article-title': 'Localized BMP-4 mediates dorsal/ventral patterning in the early Xenopus embryo', 'volume': '169', 'author': 'Schmidt', 'year': '1995', 'journal-title': 'Development'} / Development / Localized BMP-4 mediates dorsal/ventral patterning in the early Xenopus embryo by Schmidt (1995)
  44. 10.1101/gad.7.1.1 / Genes Dev / The frog prince-ss: A molecular formula for dorsoventral patterning in Xenopus by Sive (1993)
  45. {'key': '2025021322490844800_DEVELOP_122_5_1545C45', 'first-page': '289', 'article-title': 'Regional biosynthetic markers in the early amphibian embryo', 'volume': '80', 'author': 'Slack', 'year': '1984', 'journal-title': 'J. Embryo. Exp. Morph'} / J. Embryo. Exp. Morph / Regional biosynthetic markers in the early amphibian embryo by Slack (1984)
  46. {'key': '2025021322490844800_DEVELOP_122_5_1545C46', 'first-page': '283', 'article-title': 'An interaction between dorsal and ventral regions of the marginal zone in early amphibian embryos', 'volume': '56', 'author': 'Slack', 'year': '1980', 'journal-title': 'J. Embryol. Exp. Morph'} / J. Embryol. Exp. Morph / An interaction between dorsal and ventral regions of the marginal zone in early amphibian embryos by Slack (1980)
  47. 10.1006/dbio.1994.1031 / Dev. Biol / The Einsteck-method: position and structure of projections formed by implants of a ventral character by Slack (1994)
  48. 10.1038/345729a0 / Nature / Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A by Smith (1990)
  49. {'key': '2025021322490844800_DEVELOP_122_5_1545C49', 'first-page': '299', 'article-title': 'Dorsalization and neural induction: properties of the organizer in Xenopus laevis', 'volume': '78', 'author': 'Smith', 'year': '1983', 'journal-title': 'J. Embryol. Exp. Morph'} / J. Embryol. Exp. Morph / Dorsalization and neural induction: properties of the organizer in Xenopus laevis by Smith (1983)
  50. 10.1111/j.1432-0436.1985.tb00302.x / Differentiation / Biochemical specificity of Xenopus notochord by Smith (1985)
  51. 10.1016/0092-8674(92)90316-5 / Cell / Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos by Smith (1992)
  52. 10.1016/0092-8674(95)90050-0 / Cell / A nodal-related gene defines a physical and functional domain within the Spemann Organizer by Smith (1995)
  53. 10.1038/361547a0 / Nature / Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm by Smith (1993)
  54. 10.1073/pnas.91.22.10255 / Proc. Natl. Acad. Sci. USA / A truncated BMP receptor affects dorso-ventral patterning in the early Xenopus embryo by Suzuki (1994)
  55. 10.1046/j.1440-169X.1995.t01-3-00013.x / Develop. Growth Differ / Bone morphogenetic protein acts as a ventral mesoderm modifier in early Xenopus embryos by Suzuki (1995)
  56. 10.1016/0092-8674(90)90445-K / Cell / Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures by Thomsen (1990)
  57. 10.1016/0092-8674(93)80045-G / Cell / Processed Vg1 protein is an axial mesoderm inducer in Xenopus by Thomsen (1993)
  58. 10.1101/gad.7.3.355 / Genes Dev / Induction of the Xenopus organizer: expression and regulation of Xnot, a novel FGF and activin-regulated homeobox gene by von Dassow (1993)
  59. 10.1038/376331a0 / Nature / Induction of epidermis and inhibition of neural fate by BMP-4 by Wilson (1995)
  60. 10.1006/bbrc.1995.1958 / Biochem. Biophys. Res. Comm / A dominant negative bone morphogenetic protein 4 receptor causes neuralization in Xenopus ectoderm by Xu (1995)
Dates
Type When
Created 4 years, 4 months ago (April 25, 2021, 10:36 p.m.)
Deposited 6 months, 2 weeks ago (Feb. 13, 2025, 5:49 p.m.)
Indexed 3 months, 4 weeks ago (May 1, 2025, 5:44 a.m.)
Issued 29 years, 3 months ago (May 1, 1996)
Published 29 years, 3 months ago (May 1, 1996)
Published Online 29 years, 3 months ago (May 1, 1996)
Published Print 29 years, 3 months ago (May 1, 1996)
Funders 0

None

@article{Jones_1996, title={Bone morphogenetic protein-4 (BMP-4) acts during gastrula stages to cause ventralization of Xenopus embryos}, volume={122}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.122.5.1545}, DOI={10.1242/dev.122.5.1545}, number={5}, journal={Development}, publisher={The Company of Biologists}, author={Jones, C. Michael and Dale, Leslie and Hogan, Brigid L. M. and Wright, Christopher V. E. and Smith, J. C.}, year={1996}, month=may, pages={1545–1554} }