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. 1994 Oct 3;13(19):4469–4481. doi: 10.1002/j.1460-2075.1994.tb06769.x

eFGF regulates Xbra expression during Xenopus gastrulation.

H V Isaacs 1, M E Pownall 1, J M Slack 1
PMCID: PMC395379  PMID: 7925289

Abstract

We show that, in addition to a role in mesoderm induction during blastula stages, FGF signalling plays an important role in maintaining the properties of the mesoderm in the gastrula of Xenopus laevis. eFGF is a maternally expressed secreted Xenopus FGF with potent mesoderm-inducing activity. However, it is most highly expressed in the mesoderm during gastrulation, suggesting a role after the period of mesoderm induction. eFGF is inhibited by the dominant negative FGF receptor. Embryos overexpressing the dominant negative receptor show a change of behaviour of the dorsal mesoderm such that it moves around the blastopore lip instead of elongating in an antero-posterior direction. In such embryos there is a reduction in Xbra expression during gastrulation. We show that during blastula stages eFGF and Xbra are able to activate the expression of each other, suggesting that they are components of an autocatalytic regulatory loop. Moreover, we show that Xbra expression in isolated gastrula mesoderm cells is maintained by eFGF, suggesting that eFGF continues to regulate the expression of Xbra in the blastopore region. In addition, overexpression of eFGF after the mid-blastula transition results in the up-regulation of Xbra expression during gastrula stages and causes suppression of the head and enlargement of the proctodeum, which is the converse of the posterior reductions of the FGF dominant negative receptor phenotype. These data suggest an important role for eFGF in regulating the expression of Xbra and for the eFGF-Xbra regulatory pathway in the control of mesodermal cell behaviour during gastrula stages.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Amaya E., Stein P. A., Musci T. J., Kirschner M. W. FGF signalling in the early specification of mesoderm in Xenopus. Development. 1993 Jun;118(2):477–487. doi: 10.1242/dev.118.2.477. [DOI] [PubMed] [Google Scholar]
  3. Beddington R. S., Rashbass P., Wilson V. Brachyury--a gene affecting mouse gastrulation and early organogenesis. Dev Suppl. 1992:157–165. [PubMed] [Google Scholar]
  4. Carrasco A. E., Malacinski G. M. Localization of Xenopus homoeo-box gene transcripts during embryogenesis and in the adult nervous system. Dev Biol. 1987 May;121(1):69–81. doi: 10.1016/0012-1606(87)90139-4. [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. 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]
  7. Condie B. G., Harland R. M. Posterior expression of a homeobox gene in early Xenopus embryos. Development. 1987 Sep;101(1):93–105. [PubMed] [Google Scholar]
  8. Cornell R. A., Kimelman D. Activin-mediated mesoderm induction requires FGF. Development. 1994 Feb;120(2):453–462. doi: 10.1242/dev.120.2.453. [DOI] [PubMed] [Google Scholar]
  9. Cunliffe V., Smith J. C. Ectopic mesoderm formation in Xenopus embryos caused by widespread expression of a Brachyury homologue. Nature. 1992 Jul 30;358(6385):427–430. doi: 10.1038/358427a0. [DOI] [PubMed] [Google Scholar]
  10. Dale L., Matthews G., Colman A. Secretion and mesoderm-inducing activity of the TGF-beta-related domain of Xenopus Vg1. EMBO J. 1993 Dec;12(12):4471–4480. doi: 10.1002/j.1460-2075.1993.tb06136.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dohrmann C. E., Hemmati-Brivanlou A., Thomsen G. H., Fields A., Woolf T. M., Melton D. A. Expression of activin mRNA during early development in Xenopus laevis. Dev Biol. 1993 Jun;157(2):474–483. doi: 10.1006/dbio.1993.1150. [DOI] [PubMed] [Google Scholar]
  12. Essex L. J., Mayor R., Sargent M. G. Expression of Xenopus snail in mesoderm and prospective neural fold ectoderm. Dev Dyn. 1993 Oct;198(2):108–122. doi: 10.1002/aja.1001980205. [DOI] [PubMed] [Google Scholar]
  13. Godsave S. F., Isaacs H. V., Slack J. M. Mesoderm-inducing factors: a small class of molecules. Development. 1988 Mar;102(3):555–566. doi: 10.1242/dev.102.3.555. [DOI] [PubMed] [Google Scholar]
  14. Green J. B., New H. V., Smith J. C. Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell. 1992 Nov 27;71(5):731–739. doi: 10.1016/0092-8674(92)90550-v. [DOI] [PubMed] [Google Scholar]
  15. Gurdon J. B. A community effect in animal development. Nature. 1988 Dec 22;336(6201):772–774. doi: 10.1038/336772a0. [DOI] [PubMed] [Google Scholar]
  16. Gurdon J. B., Kato K., Lemaire P. The community effect, dorsalization and mesoderm induction. Curr Opin Genet Dev. 1993 Aug;3(4):662–667. doi: 10.1016/0959-437x(93)90104-w. [DOI] [PubMed] [Google Scholar]
  17. Harvey R. P. Widespread expression of MyoD genes in Xenopus embryos is amplified in presumptive muscle as a delayed response to mesoderm induction. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9198–9202. doi: 10.1073/pnas.88.20.9198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hemmati-Brivanlou A., Melton D. A. A truncated activin receptor inhibits mesoderm induction and formation of axial structures in Xenopus embryos. Nature. 1992 Oct 15;359(6396):609–614. doi: 10.1038/359609a0. [DOI] [PubMed] [Google Scholar]
  19. Herrmann B. G., Labeit S., Poustka A., King T. R., Lehrach H. Cloning of the T gene required in mesoderm formation in the mouse. Nature. 1990 Feb 15;343(6259):617–622. doi: 10.1038/343617a0. [DOI] [PubMed] [Google Scholar]
  20. Isaacs H. V., Tannahill D., Slack J. M. Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification. Development. 1992 Mar;114(3):711–720. doi: 10.1242/dev.114.3.711. [DOI] [PubMed] [Google Scholar]
  21. Keller R., Shih J., Domingo C. The patterning and functioning of protrusive activity during convergence and extension of the Xenopus organiser. Dev Suppl. 1992:81–91. [PubMed] [Google Scholar]
  22. Kimelman D., Abraham J. A., Haaparanta T., Palisi T. M., Kirschner M. W. The presence of fibroblast growth factor in the frog egg: its role as a natural mesoderm inducer. Science. 1988 Nov 18;242(4881):1053–1056. doi: 10.1126/science.3194757. [DOI] [PubMed] [Google Scholar]
  23. Kimelman D., Kirschner M. Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo. Cell. 1987 Dec 4;51(5):869–877. doi: 10.1016/0092-8674(87)90110-3. [DOI] [PubMed] [Google Scholar]
  24. Kimelman D., Maas A. Induction of dorsal and ventral mesoderm by ectopically expressed Xenopus basic fibroblast growth factor. Development. 1992 Jan;114(1):261–269. doi: 10.1242/dev.114.1.261. [DOI] [PubMed] [Google Scholar]
  25. Krieg P. A., Melton D. A. Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. Nucleic Acids Res. 1984 Sep 25;12(18):7057–7070. doi: 10.1093/nar/12.18.7057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. LaBonne C., Whitman M. Mesoderm induction by activin requires FGF-mediated intracellular signals. Development. 1994 Feb;120(2):463–472. doi: 10.1242/dev.120.2.463. [DOI] [PubMed] [Google Scholar]
  27. Paterno G. D., Gillespie L. L., Dixon M. S., Slack J. M., Heath J. K. Mesoderm-inducing properties of INT-2 and kFGF: two oncogene-encoded growth factors related to FGF. Development. 1989 May;106(1):79–83. doi: 10.1242/dev.106.1.79. [DOI] [PubMed] [Google Scholar]
  28. Ruiz i Altaba A., Melton D. A. Bimodal and graded expression of the Xenopus homeobox gene Xhox3 during embryonic development. Development. 1989 May;106(1):173–183. doi: 10.1242/dev.106.1.173. [DOI] [PubMed] [Google Scholar]
  29. Sargent M. G., Bennett M. F. Identification in Xenopus of a structural homologue of the Drosophila gene snail. Development. 1990 Aug;109(4):967–973. doi: 10.1242/dev.109.4.967. [DOI] [PubMed] [Google Scholar]
  30. Schulte-Merker S., van Eeden F. J., Halpern M. E., Kimmel C. B., Nüsslein-Volhard C. no tail (ntl) is the zebrafish homologue of the mouse T (Brachyury) gene. Development. 1994 Apr;120(4):1009–1015. doi: 10.1242/dev.120.4.1009. [DOI] [PubMed] [Google Scholar]
  31. Shishido E., Higashijima S., Emori Y., Saigo K. Two FGF-receptor homologues of Drosophila: one is expressed in mesodermal primordium in early embryos. Development. 1993 Feb;117(2):751–761. doi: 10.1242/dev.117.2.751. [DOI] [PubMed] [Google Scholar]
  32. Slack J. M., Darlington B. G., Heath J. K., Godsave S. F. Mesoderm induction in early Xenopus embryos by heparin-binding growth factors. Nature. 1987 Mar 12;326(6109):197–200. doi: 10.1038/326197a0. [DOI] [PubMed] [Google Scholar]
  33. Slack J. M., Isaacs H. V., Darlington B. G. Inductive effects of fibroblast growth factor and lithium ion on Xenopus blastula ectoderm. Development. 1988 Jul;103(3):581–590. doi: 10.1242/dev.103.3.581. [DOI] [PubMed] [Google Scholar]
  34. Slack J. M., Isaacs H. V., Johnson G. E., Lettice L. A., Tannahill D., Thompson J. Specification of the body plan during Xenopus gastrulation: dorsoventral and anteroposterior patterning of the mesoderm. Dev Suppl. 1992:143–149. [PubMed] [Google Scholar]
  35. Smith J. C., Price B. M., Green J. B., Weigel D., Herrmann B. G. Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction. Cell. 1991 Oct 4;67(1):79–87. doi: 10.1016/0092-8674(91)90573-h. [DOI] [PubMed] [Google Scholar]
  36. Smith W. C., Harland R. M. Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Cell. 1992 Sep 4;70(5):829–840. doi: 10.1016/0092-8674(92)90316-5. [DOI] [PubMed] [Google Scholar]
  37. Smith W. C., Knecht A. K., Wu M., Harland R. M. Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm. Nature. 1993 Feb 11;361(6412):547–549. doi: 10.1038/361547a0. [DOI] [PubMed] [Google Scholar]
  38. Tannahill D., Isaacs H. V., Close M. J., Peters G., Slack J. M. Developmental expression of the Xenopus int-2 (FGF-3) gene: activation by mesodermal and neural induction. Development. 1992 Jul;115(3):695–702. doi: 10.1242/dev.115.3.695. [DOI] [PubMed] [Google Scholar]
  39. Thompson J., Slack J. M. Over-expression of fibroblast growth factors in Xenopus embryos. Mech Dev. 1992 Sep;38(3):175–182. doi: 10.1016/0925-4773(92)90051-k. [DOI] [PubMed] [Google Scholar]
  40. Thomsen G. H., Melton D. A. Processed Vg1 protein is an axial mesoderm inducer in Xenopus. Cell. 1993 Aug 13;74(3):433–441. doi: 10.1016/0092-8674(93)80045-g. [DOI] [PubMed] [Google Scholar]
  41. Thomsen G., Woolf T., Whitman M., Sokol S., Vaughan J., Vale W., Melton D. A. Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures. Cell. 1990 Nov 2;63(3):485–493. doi: 10.1016/0092-8674(90)90445-k. [DOI] [PubMed] [Google Scholar]
  42. Wilson P., Keller R. Cell rearrangement during gastrulation of Xenopus: direct observation of cultured explants. Development. 1991 May;112(1):289–300. doi: 10.1242/dev.112.1.289. [DOI] [PubMed] [Google Scholar]
  43. 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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