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. 1994 Nov 1;13(21):5015–5025. doi: 10.1002/j.1460-2075.1994.tb06830.x

On the function of BMP-4 in patterning the marginal zone of the Xenopus embryo.

A Fainsod 1, H Steinbeisser 1, E M De Robertis 1
PMCID: PMC395447  PMID: 7957067

Abstract

Bone morphogenetic protein 4 (BMP-4) is expressed in the ventral marginal zone of the gastrulating embryo. At late gastrula stage this gene is expressed in the ventral-most part of the slit blastopore and in tissues that derive from it. At tailbud stages BMP-4 is expressed in the spinal cord roof plate, neural crest, eye and auditory vesicle. The interactions of BMP-4 with dorsal genes such as goosecoid (gsc) and Xnot-2 were studied in vivo. In embryos ventralized by UV irradiation and suramin treatment, BMP-4 zygotic transcripts accumulate prematurely and the entire marginal zone expresses this gene. The patterning effect of BMP-4 on ventro-posterior development can be revealed by a sensitive assay involving the injection of BMP-4 mRNA in the ventral marginal zone of embryos partially dorsalized with LiCl, which leads to the complete rescue of trunk and tail structures. The experiments presented here argue that BMP-4 may act in vivo as a ventral signal for the proper patterning of the marginal zone, actively interacting with dorsal genes such as gsc and Xnot-2. A model is proposed in which the timing of expression of various marginal zone-specific genes plays a central role in patterning the mesoderm.

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Selected References

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  1. Amaya E., Musci T. J., Kirschner M. W. Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell. 1991 Jul 26;66(2):257–270. doi: 10.1016/0092-8674(91)90616-7. [DOI] [PubMed] [Google Scholar]
  2. Basler K., Edlund T., Jessell T. M., Yamada T. Control of cell pattern in the neural tube: regulation of cell differentiation by dorsalin-1, a novel TGF beta family member. Cell. 1993 May 21;73(4):687–702. doi: 10.1016/0092-8674(93)90249-p. [DOI] [PubMed] [Google Scholar]
  3. Blumberg B., Wright C. V., De Robertis E. M., Cho K. W. Organizer-specific homeobox genes in Xenopus laevis embryos. Science. 1991 Jul 12;253(5016):194–196. doi: 10.1126/science.1677215. [DOI] [PubMed] [Google Scholar]
  4. Chakrabarti A., Matthews G., Colman A., Dale L. Secretory and inductive properties of Drosophila wingless protein in Xenopus oocytes and embryos. Development. 1992 May;115(1):355–369. doi: 10.1242/dev.115.1.355. [DOI] [PubMed] [Google Scholar]
  5. Cho K. W., Blumberg B., Steinbeisser H., De Robertis E. M. Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid. Cell. 1991 Dec 20;67(6):1111–1120. doi: 10.1016/0092-8674(91)90288-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  7. Christian J. L., McMahon J. A., McMahon A. P., Moon R. T. Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. Development. 1991 Apr;111(4):1045–1055. doi: 10.1242/dev.111.4.1045. [DOI] [PubMed] [Google Scholar]
  8. Christian J. L., Moon R. T. Interactions between Xwnt-8 and Spemann organizer signaling pathways generate dorsoventral pattern in the embryonic mesoderm of Xenopus. Genes Dev. 1993 Jan;7(1):13–28. doi: 10.1101/gad.7.1.13. [DOI] [PubMed] [Google Scholar]
  9. Dale L., Howes G., Price B. M., Smith J. C. Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. Development. 1992 Jun;115(2):573–585. doi: 10.1242/dev.115.2.573. [DOI] [PubMed] [Google Scholar]
  10. Dale L., Slack J. M. Fate map for the 32-cell stage of Xenopus laevis. Development. 1987 Apr;99(4):527–551. doi: 10.1242/dev.99.4.527. [DOI] [PubMed] [Google Scholar]
  11. Dirksen M. L., Jamrich M. A novel, activin-inducible, blastopore lip-specific gene of Xenopus laevis contains a fork head DNA-binding domain. Genes Dev. 1992 Apr;6(4):599–608. doi: 10.1101/gad.6.4.599. [DOI] [PubMed] [Google Scholar]
  12. Gerhart J., Danilchik M., Doniach T., Roberts S., Rowning B., Stewart R. Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development. Development. 1989;107 (Suppl):37–51. doi: 10.1242/dev.107.Supplement.37. [DOI] [PubMed] [Google Scholar]
  13. Gilbert S. F., Saxén L. Spemann's organizer: models and molecules. Mech Dev. 1993 May;41(2-3):73–89. doi: 10.1016/0925-4773(93)90039-z. [DOI] [PubMed] [Google Scholar]
  14. Gont L. K., Steinbeisser H., Blumberg B., de Robertis E. M. Tail formation as a continuation of gastrulation: the multiple cell populations of the Xenopus tailbud derive from the late blastopore lip. Development. 1993 Dec;119(4):991–1004. doi: 10.1242/dev.119.4.991. [DOI] [PubMed] [Google Scholar]
  15. Grunz H. Suramin changes the fate of Spemann's organizer and prevents neural induction in Xenopus laevis. Mech Dev. 1992 Aug;38(2):133–141. doi: 10.1016/0925-4773(92)90005-5. [DOI] [PubMed] [Google Scholar]
  16. Gurdon J. B. Injected nuclei in frog oocytes: fate, enlargement, and chromatin dispersal. J Embryol Exp Morphol. 1976 Dec;36(3):523–540. [PubMed] [Google Scholar]
  17. Harland R. M. In situ hybridization: an improved whole-mount method for Xenopus embryos. Methods Cell Biol. 1991;36:685–695. doi: 10.1016/s0091-679x(08)60307-6. [DOI] [PubMed] [Google Scholar]
  18. Jones C. M., Lyons K. M., Hogan B. L. Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development. 1991 Feb;111(2):531–542. doi: 10.1242/dev.111.2.531. [DOI] [PubMed] [Google Scholar]
  19. Jones C. M., Lyons K. M., Lapan P. M., Wright C. V., Hogan B. L. DVR-4 (bone morphogenetic protein-4) as a posterior-ventralizing factor in Xenopus mesoderm induction. Development. 1992 Jun;115(2):639–647. doi: 10.1242/dev.115.2.639. [DOI] [PubMed] [Google Scholar]
  20. Kao K. R., Elinson R. P. The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryos. Dev Biol. 1988 May;127(1):64–77. doi: 10.1016/0012-1606(88)90189-3. [DOI] [PubMed] [Google Scholar]
  21. Kimelman D., Christian J. L., Moon R. T. Synergistic principles of development: overlapping patterning systems in Xenopus mesoderm induction. Development. 1992 Sep;116(1):1–9. doi: 10.1242/dev.116.Supplement.1. [DOI] [PubMed] [Google Scholar]
  22. Knöchel S., Lef J., Clement J., Klocke B., Hille S., Köster M., Knöchel W. Activin A induced expression of a fork head related gene in posterior chordamesoderm (notochord) of Xenopus laevis embryos. Mech Dev. 1992 Aug;38(2):157–165. doi: 10.1016/0925-4773(92)90007-7. [DOI] [PubMed] [Google Scholar]
  23. Ku M., Melton D. A. Xwnt-11: a maternally expressed Xenopus wnt gene. Development. 1993 Dec;119(4):1161–1173. doi: 10.1242/dev.119.4.1161. [DOI] [PubMed] [Google Scholar]
  24. Köster M., Plessow S., Clement J. H., Lorenz A., Tiedemann H., Knöchel W. Bone morphogenetic protein 4 (BMP-4), a member of the TGF-beta family, in early embryos of Xenopus laevis: analysis of mesoderm inducing activity. Mech Dev. 1991 Mar;33(3):191–199. doi: 10.1016/0925-4773(91)90027-4. [DOI] [PubMed] [Google Scholar]
  25. Moody S. A. Fates of the blastomeres of the 32-cell-stage Xenopus embryo. Dev Biol. 1987 Aug;122(2):300–319. doi: 10.1016/0012-1606(87)90296-x. [DOI] [PubMed] [Google Scholar]
  26. Newport J., Kirschner M. A major developmental transition in early Xenopus embryos: I. characterization and timing of cellular changes at the midblastula stage. Cell. 1982 Oct;30(3):675–686. doi: 10.1016/0092-8674(82)90272-0. [DOI] [PubMed] [Google Scholar]
  27. Niehrs C., Steinbeisser H., De Robertis E. M. Mesodermal patterning by a gradient of the vertebrate homeobox gene goosecoid. Science. 1994 Feb 11;263(5148):817–820. doi: 10.1126/science.7905664. [DOI] [PubMed] [Google Scholar]
  28. Nishimatsu S., Suzuki A., Shoda A., Murakami K., Ueno N. Genes for bone morphogenetic proteins are differentially transcribed in early amphibian embryos. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1487–1495. doi: 10.1016/s0006-291x(05)81574-8. [DOI] [PubMed] [Google Scholar]
  29. O'Keefe H. P., Melton D. A., Ferreiro B., Kintner C. In situ hyridization. Methods Cell Biol. 1991;36:443–463. [PubMed] [Google Scholar]
  30. Oschwald R., Clement J. H., Knöchel W., Grunz H. Suramin prevents transcription of dorsal marker genes in Xenopus laevis embryos, isolated dorsal blastopore lips and activin A induced animal caps. Mech Dev. 1993 Oct;43(2-3):121–133. doi: 10.1016/0925-4773(93)90030-2. [DOI] [PubMed] [Google Scholar]
  31. Papkoff J., Schryver B. Secreted int-1 protein is associated with the cell surface. Mol Cell Biol. 1990 Jun;10(6):2723–2730. doi: 10.1128/mcb.10.6.2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ruiz i Altaba A., Jessell T. M. Pintallavis, a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis. Development. 1992 Sep;116(1):81–93. doi: 10.1242/dev.116.Supplement.81. [DOI] [PubMed] [Google Scholar]
  33. Sasai Y., Kageyama R., Tagawa Y., Shigemoto R., Nakanishi S. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev. 1992 Dec;6(12B):2620–2634. doi: 10.1101/gad.6.12b.2620. [DOI] [PubMed] [Google Scholar]
  34. Scharf S. R., Gerhart J. C. Determination of the dorsal-ventral axis in eggs of Xenopus laevis: complete rescue of uv-impaired eggs by oblique orientation before first cleavage. Dev Biol. 1980 Sep;79(1):181–198. doi: 10.1016/0012-1606(80)90082-2. [DOI] [PubMed] [Google Scholar]
  35. Sive H. L. The frog prince-ss: a molecular formula for dorsoventral patterning in Xenopus. Genes Dev. 1993 Jan;7(1):1–12. doi: 10.1101/gad.7.1.1. [DOI] [PubMed] [Google Scholar]
  36. Slack J. M. Embryonic induction. Mech Dev. 1993 May;41(2-3):91–107. doi: 10.1016/0925-4773(93)90040-5. [DOI] [PubMed] [Google Scholar]
  37. Smith J. C. Mesoderm-inducing factors in early vertebrate development. EMBO J. 1993 Dec;12(12):4463–4470. doi: 10.1002/j.1460-2075.1993.tb06135.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Smith W. C., Harland R. M. Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center. Cell. 1991 Nov 15;67(4):753–765. doi: 10.1016/0092-8674(91)90070-f. [DOI] [PubMed] [Google Scholar]
  39. Taira M., Jamrich M., Good P. J., Dawid I. B. The LIM domain-containing homeo box gene Xlim-1 is expressed specifically in the organizer region of Xenopus gastrula embryos. Genes Dev. 1992 Mar;6(3):356–366. doi: 10.1101/gad.6.3.356. [DOI] [PubMed] [Google Scholar]
  40. von Dassow G., Schmidt J. E., Kimelman D. Induction of the Xenopus organizer: expression and regulation of Xnot, a novel FGF and activin-regulated homeo box gene. Genes Dev. 1993 Mar;7(3):355–366. doi: 10.1101/gad.7.3.355. [DOI] [PubMed] [Google Scholar]

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