Abstract
ABSTRACT Mesoderm induction during Xenopus development has been extensively studied, and two members of the transforming growth factor-β family, activin βB and Vg1, have emerged as candidates for a natural inducer of dorsal mesoderm. Heretofore, analysis of Vg1 activity has relied on injection of hybrid Vg1 mRNAs, which have not been shown to direct efficient secretion of ligand and, therefore, the mechanism of mesoderm induction by processed Vg1 protein is unclear. This report describes injection of Xenopus oocytes with a chimeric activin-Vg1 mRNA, encoding the pro-region of activin βB fused to the mature region of Vg1, resulting in the processing and secretion of mature Vg1. Treatment of animal pole explants with mature Vg1 protein resulted in differentiation of dorsal, but not ventral, mesodermal tissues and dose-dependent activation of both dorsal and ventrolateral mesodermal markers. At high doses, mature Vg1 induced formation of ‘embryoids’ with a rudimentary axial pattern, head structures including eyes and a functional neuromuscular system. Furthermore, truncated forms of the activin and FGF receptors, which block mesoderm induction in the intact embryo, fully inhibited mature Vg1 activity. To examine the mechanism of inhibition, we have performed receptor-binding assays with radiolabeled Vg1. Finally, follistatin, a specific inhibitor of activin βB which is shown not to block endogenous dorsal mesoderm induction, failed to inhibit Vg1. The results support a role for endogenous Vg1 in dorsal mesoderm induction during Xenopus development.
References
66
Referenced
127
10.1016/0092-8674(91)90616-7
/ Cell / Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos by Amaya (1991)10.1073/pnas.88.15.6511
/ Proc. Natl. Acad. Sci. USA / Presence of activin (erythroid differentiation factor) in unfertilized eggs and blastulae of Xenopus laevis by Asashima (1991)10.1126/science.1677215
/ Science / Organizer-specific homeobox genes in Xenopus laevis embryos by Blumberg (1991)10.1007/BF00575837
/ Roux Arch. EntwMech. Org. / The formation of the mesoderm in urodelean amphibians. V. Its regional induction by the endoderm by Boterenbrood (1973)10.1242/dev.111.4.1045
/ Development / Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm inducing factors may play a role in ventral mesodermal patterning during embryogenesis by Christian (1991)10.1242/dev.120.2.453
/ Development / Activin-mediated mesoderm induction requires FGF by Cornell (1994)10.1242/dev.100.2.279
/ Development / Regional specification within the mesoderm of early embryos of Xenopus laevis by Dale (1987)10.1002/j.1460-2075.1989.tb03473.x
/ EMBO J. / Developmental expression of the protein product of Vg1, a localized maternal mRNA in the frog Xenopus laevis by Dale (1989)10.1002/j.1460-2075.1993.tb06136.x
/ EMBO J. / Secretion and mesoderm-inducing activity of the TGF-β-related domain of Xenopus Vg1 by Dale (1993)10.1016/0012-1606(88)90281-3
/ Dev. Biol. / A transient array of parallel microtubules in frog eggs: potential tracks for a cytoplasmic rotation that specifies the dorso-ventral axis by Elinson (1988)10.1111/j.1440-169X.1989.00423.x
/ Dev. Growth Diff. / The location of dorsal information in frog early development by Elinson (1989){'key': '2025011514162438500_DEVELOP_121_7_2155C12', 'first-page': '3610', 'article-title': 'Isolation of monoclonal antibodies specific for human c-myc protooncogene product', 'volume': '5', 'author': 'Evan', 'year': '1985', 'journal-title': 'Mol. Cell Biol.'}
/ Mol. Cell Biol. / Isolation of monoclonal antibodies specific for human c-myc protooncogene product by Evan (1985)10.1006/dbio.1993.1227
/ Dev. Biol. / Isolation and characterization of Xenopus follistatin and activin by Fukui (1993)10.1006/dbio.1994.1143
/ Dev. Biol. / Identification of activins A, AB, and B and follistatin proteins in Xenopus embryos by Fukui (1994)10.1242/dev.107.Supplement.37
/ Development / Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development by Gerhart (1989)10.1016/0012-1606(84)90042-3
/ Dev. Biol. / Early cellular interactions promote embryonic axis formation in Xenopus laevis by Gimlich (1984)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)10.1126/science.2315700
/ Science / Requirement for activin A and transforming growth factor-β1 pro-regions in homodimer assembly by Gray (1990)10.1016/0092-8674(94)90320-4
/ Cell / Follistatin, an antagonist of activin, is present in the Spemann organizer and displays direct neuralizing activity by Hemmati-Brivanlou (1994)10.1038/359609a0
/ Nature / A truncated activin receptor dominantly inhibits mesoderm induction and formation of axial structures in Xenopus embryos by Hemmati-Brivanlou (1992)10.1242/dev.101.3.557
/ Development / The development of animal cap cells in Xenopus: a measure of the start of animal cap competence to form mesoderm by Jones (1987)10.1007/BF02427884
/ Roux’s Arch. Dev. Biol. / The possible role of mesodermal growth factors in the formation of endoderm in Xenopus laevis by Jones (1993)10.1016/0012-1606(90)90365-P
/ Dev. Biol. / Spatial distribution of the capacity to initiate a secondary embryo in the 32-cell embryo of Xenopus laevis by Kageura (1990)10.1126/science.7939714
/ Science / Vertebrate embryonic induction: mesodermal and neural patterning by Kessler (1994)10.1242/dev.99.3.311
/ Development / Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction by Kintner (1987)10.1210/endo-128-3-1434
/ Endocrinology / Activin-binding protein is present in pituitary by Kogawa (1991)10.1016/0012-1606(89)90300-X
/ Dev. Biol. / The mRNA encoding elongation factor 1α (EF1α) is a major transcript at the mid-blastula transition in Xenopus by Krieg (1989)10.1016/0076-6879(87)55027-3
/ Meth. Enzymol. / In vitro RNA synthesis with SP6 RNA polymerase by Krieg (1987)10.1242/dev.120.2.463
/ Development / Mesoderm induction by activin requires FGF-mediated intracellular signals by LaBonne (1994)10.1016/0962-8924(94)90202-X
/ Trends Cell Biol. / The TGF-β family and its composite receptors by Massagué (1994)10.1038/328080a0
/ Nature / Translocation of a localized maternal mRNA to the vegetal pole of Xenopus oocytes by Melton (1987)10.1126/science.1546297
/ Science / Vegetal messenger RNA localization directed by a 340-nt sequence element in Xenopus oocytes by Mowry (1992)10.1126/science.2106159
/ Science / Activin-binding protein from rat ovary is follistatin by Nakamura (1990){'volume-title': 'Normal Table of Xenopus laevis (Daudin)', 'year': '1967', 'author': 'Nieuwkoop', 'key': '2025011514162438500_DEVELOP_121_7_2155C34'}
/ Normal Table of Xenopus laevis (Daudin) by Nieuwkoop (1967)10.1007/BF00578701
/ Roux Arch. EntwMech. Org. / The formation of mesoderm in urodelean amphibians. I. Induction by the endoderm by Nieuwkoop (1969)10.1007/BF00577017
/ Roux Arch. EntwMech. Org. / The formation of the mesoderm in urodelean amphibians II. The origin of the dorso-ventral polarity of the mesoderm by Nieuwkoop (1969)10.3109/08977199309011020
/ Growth Factors / Immunodetection of Xenopus bone morphogenetic protein-4 in early embryos by Nishimatsu (1993)10.1016/S0091-679X(08)60301-5
/ Xenopus laevis: Practical Uses in Cell and Molecular Biology by Peng (1991)10.1016/0092-8674(85)90273-9
/ Cell / Identification and cloning of localized maternal mRNAs from Xenopus eggs by Rebagliati (1985)10.1016/0092-8674(94)90068-X
/ Cell / Xenopus chordin: a novel drosalizing factor activated by organizer-specific homeobox genes by Sasai (1994)10.1002/j.1460-2075.1994.tb06660.x
/ EMBO J. / Effects of truncated activin and FGF receptors and of follistatin on the inducing activities of BVg1 and activin: does activin play a role in mesoderm induction? by Schulte-Merker (1994)10.1242/dev.113.2.661
/ Development / The nature of the mesoderm-inducing signal in Xenopus: a transfilter induction study by Slack (1991){'key': '2025011514162438500_DEVELOP_121_7_2155C43', 'first-page': '143', 'article-title': 'Specification of the body plan during Xenopus gastrulation: dorsoventral and anteroposterior patterning of the mesoderm', 'author': 'Slack', 'year': '1992', 'journal-title': 'Development Suppl.'}
/ Development Suppl. / Specification of the body plan during Xenopus gastrulation: dorsoventral and anteroposterior patterning of the mesoderm by Slack (1992){'key': '2025011514162438500_DEVELOP_121_7_2155C44', '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)10.1016/0092-8674(91)90573-H
/ Cell / Expression of a Xenopus homolog of Brachyury (T) in an immediate-early response to mesoderm induction by Smith (1991)10.1016/0092-8674(91)90070-F
/ Cell / Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center by Smith (1991)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)10.1038/361547a0
/ Nature / Secreted noggin protein mimics the Spemann organizer in dorsalizing Xenopus mesoderm by Smith (1993)10.1126/science.2382134
/ Science / A mouse macrophage factor induces head structures and organizes a body axis in Xenopus by Sokol (1990)10.1016/0092-8674(91)90069-B
/ Cell / Injected wnt RNA induces a complete body axis in Xenopus embryos by Sokol (1991)10.1016/0022-2836(86)90438-9
/ J. Mol. Biol. / Isolation and characterization of sarcomeric actin genes expressed in Xenopus laevis embryos by Stutz (1986)10.1007/BF00650029
/ Roux Arch. EntwMech. Org. / Mesoderm formation in the anuran Xenopus laevis (Daudin by Sudarwati (1971)10.1073/pnas.91.22.10255
/ Proc. Natl. Acad. Sci. U.S.A. / A truncated BMP receptor affects dorsal-ventral patterning in the early Xenopus embryo by Suzuki (1994)10.1242/dev.101.2.339
/ Development / Gastrulation movements provide an early marker of mesoderm induction in Xenopus laevis by Symes (1987)10.1242/dev.106.4.775
/ Development / Localized synthesis of the Vg1 protein during early Xenopus development by Tannahill (1989)10.1016/0006-291X(91)91521-D
/ Biochem. Biophy. Res. Comm. / Expression of mRNA for activin-binding protein (follistatin) during early embryonic development of Xenopus laevis by Tashiro (1991)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)10.1016/0092-8674(93)80045-G
/ Cell / Processed Vg1 protein is an axial mesoderm inducer in Xenopus by Thomsen (1993)10.3109/08977199209046927
/ Growth Factors / Identification of bone morphogenetic protein-2 in early Xenopus laevis embryos by Ueno (1992)10.1007/978-3-642-74781-6_8
/ Peptide growth factors and their receptors vol. 2 by Vale (1990)10.1016/0012-1606(87)90411-8
/ Dev. Biol. / Subcortical rotation in Xenopus eggs: an early step in embryonic axis specification by Vincent (1987)10.1016/0168-9525(94)90134-1
/ Trends Genet. / Vg1 and regional specification in vertebrates: a new role for an old molecule by Vize (1994)10.1016/0092-8674(87)90109-7
/ Cell / A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-β by Weeks (1987)10.1016/S0960-9822(00)00152-4
/ Curr. Biol. / Mesodermal patterning by an inducer gradient depends on secondary cell-cell communication by Wilson (1994)10.1111/j.1440-169X.1950.tb00042.x
/ Embryologia / Regional differentiation of the isolated ectoderm of the Triturus gastrula induced through a protein extract by Yamada (1950)10.1038/336592a0
/ Nature / The maternal mRNA Vg1 is correctly localized following injection into Xenopus oocytes by Yisraeli (1988)
Dates
Type | When |
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Created | 4 years, 4 months ago (April 25, 2021, 10:23 p.m.) |
Deposited | 7 months, 1 week ago (Jan. 15, 2025, 9:16 a.m.) |
Indexed | 1 month, 3 weeks ago (July 2, 2025, 2:48 p.m.) |
Issued | 30 years, 1 month ago (July 1, 1995) |
Published | 30 years, 1 month ago (July 1, 1995) |
Published Online | 30 years, 1 month ago (July 1, 1995) |
Published Print | 30 years, 1 month ago (July 1, 1995) |
@article{Kessler_1995, title={Induction of dorsal mesoderm by soluble, mature Vg1 protein}, volume={121}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.121.7.2155}, DOI={10.1242/dev.121.7.2155}, number={7}, journal={Development}, publisher={The Company of Biologists}, author={Kessler, Daniel S. and Melton, Douglas A.}, year={1995}, month=jul, pages={2155–2164} }