A conserved mechanism for vertebrate mesoderm specification in urodele amphibians and mammals
Open accessAbstract
Understanding how mesoderm is specified during development is a fundamental issue in biology, and it has been studied intensively in embryos from Xenopus. The gene regulatory network (GRN) for Xenopus is surprisingly complex and is not conserved in vertebrates, including mammals, which have single copies of the key genes Nodal and Mix. Why the Xenopus GRN should express multiple copies of Nodal and Mix genes is not known. To understand how these expanded gene families evolved, we investigated mesoderm specification in embryos from axolotls, representing urodele amphibians, since urodele embryology is basal to amphibians and was conserved during the evolution of amniotes, including mammals. We show that single copies of Nodal and Mix are required for mesoderm specification in axolotl embryos, suggesting the ancestral vertebrate state. Furthermore, we uncovered a novel genetic interaction in which Mix induces Brachyury expression, standing in contrast to the relationship of these molecules in Xenopus. However, we demonstrate that this functional relationship is conserved in mammals by showing that it is involved in the production of mesoderm from mouse embryonic stem cells. From our results, we produced an ancestral mesoderm (m)GRN, which we suggest is conserved in vertebrates. The results are discussed within the context of a theory in which the evolution of mechanisms governing early somatic development is constrained by the ancestral germ line-soma relationship, in which germ cells are produced by epigenesis.
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A fundamental Box II subcircuit may underlie mesoderm specification in vertebrate embryogenesis.
“Similarly, a fundamental Box II subcircuit may underlie mesoderm specification in vertebrate embryogenesis (Swiers et al., 2010).”
From Evolution of Gene Regulatory Networks Controlling Body Plan Development (2011) · cites this paper as Swiers et al., 2010
The Abstract and Discussion propose a mesoderm gene-regulatory network conserved across vertebrates, supporting the hedged claim that a fundamental circuit may underlie mesoderm specification. Our copy does not identify that network as a “Box II subcircuit,” so it does not establish the claim’s specific designation. (LLM, conf=0.78)
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Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Normal Table of Xenopus Laevis (Daudin)
Nieuwkoop, P. D., & Faber, J. (1958) · Copeia · doi:10.2307/1439568 · Cited by 4,542 · see citing works
Normal table of Xenopus laevis (Daudin)
Gurdon, J. B. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89129-5 · Cited by 2,888 · see citing works
Kitano, H. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1471 · Cited by 2,278 · see citing works
Early development of Xenopus laevis : a laboratory manual
Sive, H. L., Grainger, R. M., & Harland, R. M. (2000) · Medical Entomology and Zoology · Cited by 1,222 · see citing works
Smith, J. C., Price, B. M. J., Green, J. B. A., Weigel, D., & Herrmann, B. G. (1991) · Cell · doi:10.1016/0092-8674(91)90573-h · Cited by 971 · see citing works
Conlon, F. L., Lyons, K. M., Takaesu, N. T., Barth, K. S., Kispert, A., Herrmann, B. G., & Robertson, E. J. (1994) · Development · doi:10.1242/dev.120.7.1919 · Cited by 772 · see citing works
Shaping the Vertebrate Body Plan by Polarized Embryonic Cell Movements
Keller, R. E. (2002) · Science · doi:10.1126/science.1079478 · Cited by 716 · see citing works
Global patterns of diversification in the history of modern amphibians
Roelants, K., Gower, D. J., Wilkinson, M., Loader, S. P., Biju, S. D., Guillaume, K., Moriau, L., & Bossuyt, F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608378104 · Cited by 646 · see citing works
Nodal signaling: developmental roles and regulation
Shen, M. M. (2007) · Development · doi:10.1242/dev.000166 · Cited by 539 · see citing works
Green, J. B. A., New, H. V., & Smith, J. C. (1992) · Cell · doi:10.1016/0092-8674(92)90550-v · Cited by 482 · see citing works
Tada, S., Era, T., Furusawa, C., Sakurai, H., Nishikawa, S., Kinoshita, M., Nakao, K., Chiba, T., & Nishikawa, S.-I. (2005) · Development · doi:10.1242/dev.02005 · Cited by 456 · see citing works
Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation
Jones, C. M., Kuehn, M. R., Hogan, B. L. M., Smith, J. C., & Wright, C. V. E. (1995) · Development · doi:10.1242/dev.121.11.3651 · Cited by 419 · see citing works
Tetrapod trackways from the early Middle Devonian period of Poland
Niedźwiedzki, G., Szrek, P., Narkiewicz, K., Narkiewicz, M., & Ahlberg, P. E. (2010) · Nature · doi:10.1038/nature08623 · Cited by 296 · see citing works
Mesoderm formation in response to Brachyury requires FGF signalling
Schulte-Merker, S., & Smith, J. C. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00017-0 · Cited by 281 · see citing works
A stem batrachian from the Early Permian of Texas and the origin of frogs and salamanders
Anderson, J. S., Reisz, R. R., Scott, D. M., et al. (2008) · Nature · doi:10.1038/nature06865 · Cited by 234 · see citing works
<i>Mixl1</i>is required for axial mesendoderm morphogenesis and patterning in the murine embryo
Hart, A. H., Hartley, L., Sourris, K., Stadler, E. S., Li, R., Stanley, E. G., Tam, P. P. L., Elefanty, A. G., & Robb, L. (2002) · Development · doi:10.1242/dev.129.15.3597 · Cited by 229 · see citing works
β-Catenin/Tcf-regulated transcription prior to the midblastula transition
Yang, J., Tan, C. L., Darken, R. S., Wilson, P. A., & Klein, P. S. (2002) · Development · doi:10.1242/dev.00150 · Cited by 211 · see citing works
Mixer , a Homeobox Gene Required for Endoderm Development
Henry, G. L., & Melton, D. A. (1998) · Science · doi:10.1126/science.281.5373.91 · Cited by 204 · see citing works
Developmental Biology of the Axolotl
Bagnara, J. T., Armstrong, J., & Malacinski, G. M. (1989) · Copeia · doi:10.2307/1445526 · Cited by 201 · see citing works
Xenopus nodal-related signaling is essential for mesendodermal patterning during early embryogenesis
Osada, S., & Wright, C. V. E. (1999) · Development · doi:10.1242/dev.126.14.3229 · Cited by 186 · see citing works
Bix1, a direct target of Xenopus T-box genes, causes formation of ventral mesoderm and endoderm
Tada, M., Casey, E. S., Fairclough, L. C., & Smith, J. C. (1998) · Development · doi:10.1242/dev.125.20.3997 · Cited by 172 · see citing works
Xnr4:AXenopusNodal-Related Gene Expressed in the Spemann Organizer
Joseph, E. M., & Melton, D. A. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8510 · Cited by 164 · see citing works
Direct neural induction and selective inhibition of mesoderm and epidermis inducers by Xnr3
Ezal, C., Marion, C. D., Steele, K. A., George, S. E., & Smith, W. C. (1997) · Development · doi:10.1242/dev.124.2.483 · Cited by 161 · see citing works
Handrigan, G. R., & Wassersug, R. J. (2007) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2006.00001.x · Cited by 139 · see citing works
A genetic regulatory network for Xenopus mesendoderm formation
Loose, M., & Patient, R. K. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.04.014 · Cited by 133 · see citing works
Self-citationLemaire, P., Darras, S., Caillol, D. H., & Kodjabachian, L. (1998) · Development · doi:10.1242/dev.125.13.2371 · Cited by 127 · see citing works
Building divergent body plans with similar genetic pathways
Swalla, B. J. (2006) · Heredity · doi:10.1038/sj.hdy.6800872 · Cited by 120 · see citing works
Evolution of predetermined germ cells in vertebrate embryos: implications for macroevolution
Johnson, A. D., Drum, M., Bachvarova, R. F., et al. (2003) · Evolution & Development · doi:10.1046/j.1525-142x.2003.03048.x · Cited by 118 · see citing works
Self-citationTiming of endogenous activin-like signals and regional specification of theXenopusembryo
Lee, M. A., Heasman, J., & Whitman, M. (2001) · Development · doi:10.1242/dev.128.15.2939 · Cited by 115 · see citing works
Johnson, A. D., Bachvarova, R. F., Drum, M., et al. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0264 · Cited by 96 · see citing works
Self-citationA novel Xenopus Mix-like gene milk involved in the control of the endomesodermal fates
Ecochard, V., Cayrol, C., Rey, S., Foulquier, F., Caillol, D. H., Lemaire, P., & Duprat, A. M. (1998) · Development · doi:10.1242/dev.125.14.2577 · Cited by 87 · see citing works
Yu, J., Holland, L. Z., & Holland, N. D. (2002) · Evolution & Development · doi:10.1046/j.1525-142x.2002.02030.x · Cited by 84 · see citing works
Irion, S., Nostro, M. C., Kattman, S. J., & Keller, G. M. (2008) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2008.73.065 · Cited by 83 · see citing works
Johnson, A. D., Crother, B. I., White, M. E., et al. (2003) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2003.1331 · Cited by 80 · see citing works
Self-citationRobb, L. G., Hartley, L., Begley, C. G., Brodnicki, T. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., & Elefanty, A. G. (2000) · Developmental Dynamics · doi:10.1002/1097-0177(2000)9999:9999 · Cited by 78 · see citing works
The origin of the mesoderm in an anuran, Xenopus laevis, and a urodele, Ambystoma mexicanum
Smith, J. C., & Malacinski, G. M. (1983) · Developmental Biology · doi:10.1016/0012-1606(83)90354-8 · Cited by 73 · see citing works
Izumi, N., Era, T., Akimaru, H., Yasunaga, M., & Nishikawa, S. (2007) · Stem Cells · doi:10.1634/stemcells.2006-0681 · Cited by 70 · see citing works
Contrasting Developmental Trajectories in the Earliest Known Tetrapod Forelimbs
Callier, V., Clack, J. A., & Ahlberg, P. (2009) · Science · doi:10.1126/science.1167542 · Cited by 60 · see citing works
Shook, D. R., & Keller, R. E. (2007) · Journal of Experimental Zoology Part B Molecular and Developmental Evolution · doi:10.1002/jez.b.21198 · Cited by 57 · see citing works
Ünsal, K., & Morgan, G. T. (1995) · Journal of Molecular Biology · doi:10.1006/jmbi.1995.0262 · Cited by 57 · see citing works
Bachvarova, R. F., Crother, B. I., Manova, K., et al. (2009) · Evolution & Development · doi:10.1111/j.1525-142x.2009.00360.x · Cited by 52 · see citing works
Inhibitor-resistant type I receptors reveal specific requirements for TGF-β signaling in vivo
Ho, D. M., Chan, J. C.-Y., Bayliss, P. E., et al. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.03.050 · Cited by 50 · see citing works
Multiple nodal-Related Genes Act Coordinately in Xenopus Embryogenesis
Onuma, Y., Takahashi, S., Yokota, C., & Asashima, M. (2002) · Developmental Biology · doi:10.1006/dbio.2001.0493 · Cited by 46 · see citing works
The role ofMixerin patterning the earlyXenopusembryo
Kofron, M. J., Wylie, C., & Heasman, J. (2004) · Development · doi:10.1242/dev.01132 · Cited by 44 · see citing works
Transcriptional regulation of mesendoderm formation in Xenopus
Wardle, F. C., & Smith, J. C. (2005) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2005.11.008 · Cited by 40 · see citing works
Shook, D. R., Majer, C. R., & Keller, R. E. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0718 · Cited by 40 · see citing works
Evolution of germ cell development in tetrapods: comparison of urodeles and amniotes
Bachvarova, R. F., Crother, B. I., & Johnson, A. D. (2009) · Evolution & Development · doi:10.1111/j.1525-142x.2009.00366.x · Cited by 32 · see citing works
Self-citationBrun, R., & Garson, J. A. (1984) · Journal of Experimental Zoology · doi:10.1002/jez.1402290208 · Cited by 29 · see citing works
Crother, B. I., White, M. E., & Johnson, A. D. (2007) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2007.05.035 · Cited by 27 · see citing works
Self-citationColas, A. R., Cartry, J., Buisson, I., Umbhauer, M., Smith, J. C., & Riou, J. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.05.547 · Cited by 26 · see citing works
Molecular components of the endoderm specification pathway in Xenopus tropicalis
D'Souza, A., Lee, M. M., Taverner, N. V., Mason, J., Carruthers, S. N., Smith, J. C., Amaya, E., Papalopulu, N., & Zorn, A. M. (2002) · Developmental Dynamics · doi:10.1002/dvdy.10201 · Cited by 26 · see citing works
Nodal-related geneXnr5 is amplified in theXenopus genome
Takahashi, S., Onuma, Y., Yokota, C., Westmoreland, J. J., Asashima, M., & Wright, C. V. E. (2006) · genesis · doi:10.1002/dvg.20217 · Cited by 25 · see citing works
Regulation of apoptosis in theXenopusembryo by Bix3
Trindade, M., Messenger, N. J., Papin, C., et al. (2003) · Development · doi:10.1242/dev.00489 · Cited by 25 · see citing works
The evolutionary origin of nodal-related genes in teleosts
Xiang, F., & Dougan, S. T. (2007) · Development Genes and Evolution · doi:10.1007/s00427-007-0191-y · Cited by 20 · see citing works
Nath, K., & Elinson, R. P. (2006) · Gene Expression Patterns · doi:10.1016/j.modgep.2006.07.003 · Cited by 18 · see citing works
泉, 治. (2008) · 名古屋大学 eBooks · Cited by 13 · see citing works
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Research works printed but not linked: 1
- Turksne, K. (Ed.), 2006. Embryonic Stem Cell Protocols Volume 2: Differentiation Models. Humana Press, Totowa.
Cited by
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Evolution of Gene Regulatory Networks Controlling Body Plan Development
Peter, I. S., & Davidson, E. H. (2011) · Cell · doi:10.1016/j.cell.2011.02.017 · Cited by 417 · see citing works
- Authors
- Swiers, G., Chen, Y.-H., Johnson, A. D., & Loose, M.
- Affiliations
- University of Nottingham (GB)
- Corresponding author
- Johnson, Andrew D.
- Loose, Matthew
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 343
- Issue
- 1-2
- Pages
- 138-152
- ISSN
- 0012-1606 (ISSN-L)
- OpenAlex
- W2019140473
- Cited by
- 35
- References
- 58
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 3 · 2016: 5 · 2015: 4 · 2014: 5 · 2013: 1 · 2012: 3
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- MRC
- The Wellcome Trust
- EvoCell Ltd
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Planarian Biology and Electrostimulation
- Keywords
- mesoderm specification, Nodal signaling, Brachyury, gene regulatory networks, axolotl, urodele amphibians, mouse embryonic stem cells, epigenesis, amniote evolution
- MeSH terms
- Amphibians, Animals, Cell Differentiation, Embryo, Mammalian, Embryo, Nonmammalian, Mammals, Mesoderm, Vertebrates, Xenopus, Mice
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