The DOI matches its Crossref record; 78 of the 80 references it cites were found in a registry or an index.
The Wnt code: cnidarians signal the way
Abstract
Cnidarians are the simplest metazoans with a nervous system. They are well known for their regeneration capacity, which is based on the restoration of a signalling centre (organizer). Recent work has identified the canonical Wnt pathway in the freshwater polyp Hydra, where it acts in organizer formation and regeneration. Wnt signalling is also essential for cnidarian embryogenesis. In the sea anemone Nematostella vectensis 11 of the 12 known wnt gene subfamilies were identified. Different wnt genes exhibit serial and overlapping expression domains along the oral-aboral axis of the embryo (the 'wnt code'). This is reminiscent of the hox code (cluster) in bilaterian embryogenesis that is, however, absent in cnidarians. It is proposed that the common ancestor of cnidarians and bilaterians invented a set of wnt genes that patterned the ancient main body axis. Major antagonists of Wnt ligands (e.g. Dkk 1/2/4) that were previously known only from chordates, are also present in cnidarians and exhibit a similar conserved function. The unexpectedly high level of genetic complexity of wnt genes evolved in early multi-cellular animals about 650 Myr ago and suggests a radical expansion of the genetic repertoire, concurrent with the evolution of multi-cellularity and the diversification of eumetazoan body plans.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“or even the formation of multiple polyp heads52.”
From Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis (2014) · cites this paper as [52]
Citations
Cites
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325
Secreted antagonists of the Wnt signalling pathway
Kawano, Y., & Kypta, R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00623 · Cited by 1,584
Wnt signalling regulates adult hippocampal neurogenesis
Lie, D. C., Colamarino, S. A., Song, H., Désiré, L., Mira, H., Consiglio, A., Lein, E. S., Jessberger, S., Lansford, H., Dearie, A. R., et al. (2005) · Nature · doi:10.1038/nature04108 · Cited by 1,544
Veeman, M. T., Axelrod, J. D., & Moon, R. T. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00266-1 · Cited by 1,359
Bänziger, C., Soldini, D., Schütt, C., Zipperlen, P., Hausmann, G., & Basler, K. (2006) · Cell · doi:10.1016/j.cell.2006.02.049 · Cited by 764
WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra
Hobmayer, B., Rentzsch, F., Kuhn, K., Happel, C. M., von Laue, C. C., Snyder, P., Rothbächer, U., & Holstein, T. W. (2000) · Nature · doi:10.1038/35025063 · Cited by 599
Unexpected complexity of the Wnt gene family in a sea anemone
Kusserow, A., Pang, K., Sturm, C., Hrouda, M., Lentfer, J., Schmidt, H. A., Technau, U., von Haeseler, A., Hobmayer, B., Martindale, M. Q., et al. (2005) · Nature · doi:10.1038/nature03158 · Cited by 599
Self-citationSecretion of Wnt Ligands Requires Evi, a Conserved Transmembrane Protein
Bartscherer, K., Pelte, N., Ingelfinger, D., & Boutros, M. (2006) · Cell · doi:10.1016/j.cell.2006.04.009 · Cited by 580
Tao, Q., Yokota, C., Puck, H., Kofron, M., Birsoy, B., Yan, D., Asashima, M., Wylie, C. C., Lin, X., & Heasman, J. (2005) · Cell · doi:10.1016/j.cell.2005.01.013 · Cited by 510
The genesis and evolution of homeobox gene clusters
García‐Fernàndez, J. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1723 · Cited by 490
The ParaHox gene cluster is an evolutionary sister of the Hox gene cluster
Brooke, N. M., Garcia-Fernàndez, J., & Holland, P. W. H. (1998) · Nature · doi:10.1038/31933 · Cited by 468
Secreted Frizzled‐related proteins: searching for relationships and patterns
Jones, S. E., & Jomary, C. (2002) · BioEssays · doi:10.1002/bies.10136 · Cited by 427
Evolution of Key Cell Signaling and Adhesion Protein Families Predates Animal Origins
King, N., Hittinger, C. T., & Carroll, S. B. (2003) · Science · doi:10.1126/science.1083853 · Cited by 424
Origins of Bilateral Symmetry: Hox and Dpp Expression in a Sea Anemone
Finnerty, J. R., Pang, K., Burton, P., Paulson, D., & Martindale, M. Q. (2004) · Science · doi:10.1126/science.1091946 · Cited by 407
Martindale, M. Q., Pang, K., & Finnerty, J. R. (2004) · Development · doi:10.1242/dev.01119 · Cited by 396
González‐Sancho, J. M., Aguilera, Ó., García, J. M., Pendás-Franco, N., Peña, C., Cal, S., de Herreros, A. G., Bonilla, F., & Múñoz, A. (2004) · Oncogene · doi:10.1038/sj.onc.1208303 · Cited by 370
Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer
Aguilera, Ó., Fraga, M. F., Ballestar, E., Paz, M. F., Herranz, M., Espada, J., García, J. M., Múñoz, A., Esteller, M., & González‐Sancho, J. M. (2006) · Oncogene · doi:10.1038/sj.onc.1209439 · Cited by 340
Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians
Technau, U., Rudd, S., Maxwell, P., Gordon, P. M. K., Saina, M., Grasso, L. C., Hayward, D. C., Sensen, C. W., Saint, R., Holstein, T. W., et al. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.09.007 · Cited by 337
Self-citationKremen2 modulates Dickkopf2 activity during Wnt/lRP6 signaling
Mao, B., & Niehrs, C. (2003) · Gene · doi:10.1016/s0378-1119(02)01106-x · Cited by 325
An ancient role for nuclear β-catenin in the evolution of axial polarity and germ layer segregation
Wikramanayake, A. H., Hong, M., Lee, P. N., Pang, K., Byrum, C. A., Bince, J. M., Xu, R., & Martindale, M. Q. (2003) · Nature · doi:10.1038/nature02113 · Cited by 324
The Cambrian “explosion”: Slow-fuse or megatonnage?
Morris, S. C. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4426 · Cited by 317
Transgenic Hydra allow in vivo tracking of individual stem cells during morphogenesis
Wittlieb, J., Khalturin, K., Lohmann, J. U., Anton‐Erxleben, F., & Bosch, T. C. G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510163103 · Cited by 298
The Culture, Sexual and Asexual Reproduction, and Growth of the Sea Anemone Nematostella vectensis
Hand, C., & Uhlinger, K. R. (1992) · Biological Bulletin · doi:10.2307/1542110 · Cited by 288
Formation of the head organizer in hydra involves the canonical Wnt pathway.
Broun, M., Gee, L., Reinhardt, B., & Bode, H. R. (2005) · Development · doi:10.1242/dev.01848 · Cited by 287
The production of new hydranths in Hydra by the insertion of small grafts
Browne, E. N. (1909) · Journal of Experimental Zoology · doi:10.1002/jez.1400070102 · Cited by 275
Ancient origin of the Hox gene cluster
Ferrier, D. E. K., & Holland, P. W. H. (2001) · Nature Reviews Genetics · doi:10.1038/35047605 · Cited by 260
CKI, there's more than one: casein kinase I family members in Wnt and Hedgehog signalingPreprint
Price, M. A. (2006) · Genes & Development · doi:10.1101/gad.1394306 · Cited by 257
Cnidarians: An evolutionarily conserved model system for regeneration?
Holstein, T. W., Hobmayer, E., & Technau, U. (2003) · Developmental Dynamics · doi:10.1002/dvdy.10227 · Cited by 225
Self-citationRising starlet: the starlet sea anemone,Nematostella vectensis
Darling, J. A., Reitzel, A. M., Burton, P. M., Mazza, M. E., Ryan, J. F., Sullivan, J. C., & Finnerty, J. R. (2005) · BioEssays · doi:10.1002/bies.20181 · Cited by 214
Origin and evolution of endoderm and mesoderm
Technau, U., & Scholz, C. B. (2003) · The International Journal of Developmental Biology · doi:10.1387/ijdb.14756329 · Cited by 208
HyBra1, a Brachyury homologue, acts during head formation in Hydra
Technau, U., & Bode, H. R. (1999) · Development · doi:10.1242/dev.126.5.999 · Cited by 201
Minimal ProtoHox cluster inferred from bilaterian and cnidarian Hox complements
Chourrout, D., Delsuc, F., Chourrout, P., Edvardsen, R. B., Rentzsch, F., Renfer, E., Jensen, M. F., Zhu, B., de Jong, P., Steele, R. E., et al. (2006) · Nature · doi:10.1038/nature04863 · Cited by 197
Precambrian animal diversity: Putative phosphatized embryos from the Doushantuo Formation of China
Chen, J.-Y., Oliveri, P., Li, C.-W., Zhou, G.-Q., Gao, F., Hagadorn, J. W., Peterson, K. J., & Davidson, E. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4457 · Cited by 187
A WNT of things to come: Evolution of Wnt signaling and polarity in cnidarians
LEE, P., PANG, K., Matus, D. Q., & Martindale, M. Q. (2006) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2006.05.002 · Cited by 180
Rentzsch, F., Anton, R., Saina, M., Hammerschmidt, M., Holstein, T. W., & Technau, U. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.06.003 · Cited by 169
Self-citationAn ancient Wnt-Dickkopf antagonism inHydra
Guder, C., Pinho, S., Nacak, T. G., Schmidt, H. A., Hobmayer, B., Niehrs, C., & Holstein, T. W. (2006) · Development · doi:10.1242/dev.02265 · Cited by 168
Self-citationPrecambrian Animal Life: Probable Developmental and Adult Cnidarian Forms from Southwest China
Chen, J.-Y., Oliveri, P., Gao, F., Dornbos, S. Q., Li, C.-W., Bottjer, D. J., & Davidson, E. H. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0714 · Cited by 165
Fritzenwanker, J. H., Saina, M., & Technau, U. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.08.014 · Cited by 165
A three-tiered mechanism for regulation of planar cell polarity
Tree, D., Ma, D., & Axelrod, J. D. (2002) · Seminars in Cell and Developmental Biology · doi:10.1016/s1084-9521(02)00042-3 · Cited by 161
Genomic inventory and expression of Sox and Fox genes in the cnidarian Nematostella vectensis
Magie, C. R., Pang, K., & Martindale, M. Q. (2005) · Development Genes and Evolution · doi:10.1007/s00427-005-0022-y · Cited by 158
Parameters of self-organization in Hydra aggregates
Technau, U., von Laue, C. C., Rentzsch, F., Luft, S., Hobmayer, B., Bode, H. R., & Holstein, T. W. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.22.12127 · Cited by 156
Self-citationSpring, J., Yanze, N., Jösch, C., Middel, A. M., Winninger, B., & Schmid, V. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0616 · Cited by 152
Extavour, C. G., Pang, K., Matus, D. Q., & Martindale, M. Q. (2005) · Evolution & Development · doi:10.1111/j.1525-142x.2005.05023.x · Cited by 144
Scholz, C. B., & Technau, U. (2003) · Development Genes and Evolution · doi:10.1007/s00427-002-0272-x · Cited by 142
Hox, ParaHox, ProtoHox: facts and guesses
García‐Fernàndez, J. (2004) · Heredity · doi:10.1038/sj.hdy.6800621 · Cited by 138
Selection for genes encoding secreted proteins and receptors.
Klein, R. D., Gu, Q., Goddard, A. D., & Rosenthal, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.14.7108 · Cited by 136
Matus, D. Q., Thomsen, G. H., & Martindale, M. Q. (2006) · Current Biology · doi:10.1016/j.cub.2006.01.052 · Cited by 129
Characterization of the head organizer in hydra
Broun, M., & Bode, H. R. (2002) · Development · doi:10.1242/dev.129.4.875 · Cited by 127
Cnidarians and ancestral genetic complexity in the animal kingdom
Miller, D. J., Ball, E. E., & Technau, U. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.08.002 · Cited by 123
Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning
Davidson, G., Mao, B., del Barco Barrantes, I., & Niehrs, C. (2002) · Development · doi:10.1242/dev.00154 · Cited by 120
Phylogenetic Analysis of the Wnt Gene Family
Prud’homme, B., Lartillot, N., Balavoine, G., Adoutte, A., & Vervoort, M. (2002) · Current Biology · doi:10.1016/s0960-9822(02)01068-0 · Cited by 116
Totipotent migratory stem cells in a hydroid
Müller, W. A., Teo, R., & Frank, U. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.08.006 · Cited by 116
Axial Patterning and Diversification in the Cnidaria Predate the Hox System
Kamm, K., Schierwater, B., Jakob, W., Dellaporta, S. L., & Miller, D. J. (2006) · Current Biology · doi:10.1016/j.cub.2006.03.036 · Cited by 116
The Mesoderm Specification Factor Twist in the Life Cycle of Jellyfish
Spring, J., Yanze, N., Middel, A. M., Stierwald, M., Gröger, H., & Schmid, V. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9956 · Cited by 115
Wnts and wing: Wnt signaling in vertebrate limb development and musculoskeletal morphogenesis
Yang, Y. (2003) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.10026 · Cited by 113
Planar Polarity Is Positively Regulated by Casein Kinase Iɛ in Drosophila
Strutt, H. L., Price, M. A., & Strutt, D. I. (2006) · Current Biology · doi:10.1016/j.cub.2006.04.041 · Cited by 97
Plickert, G., Jacoby, V., Uri Frank, A., Müller, W. A., & Mokady, O. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.06.043 · Cited by 97
Dickkopf related genes are components of the positional value gradient in Hydra
Augustin, R., Franke, A., Khalturin, K., Kiko, R., Siebert, S., Hemmrich, G., & Bosch, T. C. G. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.04.003 · Cited by 96
Heads or Tails? Amphioxus and the Evolution of Anterior–Posterior Patterning in Deuterostomes
Holland, L. Z. (2002) · Developmental Biology · doi:10.1006/dbio.2001.0503 · Cited by 94
An evolutionary conserved role of Wnt signaling in stem cell fate decision
Teo, R., Möhrlen, F., Plickert, G., Müller, W. A., & Frank, U. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.10.009 · Cited by 89
Pattern Formation in Hydra vulgaris Is Controlled by Lithium-Sensitive Processes
Hassel, M., Albert, K., & Hofheinz, S. (1993) · Developmental Biology · doi:10.1006/dbio.1993.1083 · Cited by 60
A Dickkopf-3-related gene is expressed in differentiating nematocytes in the basal metazoan Hydra
Fedders, H., Augustin, R., & Bosch, T. C. G. (2004) · Development Genes and Evolution · doi:10.1007/s00427-003-0378-9 · Cited by 59
Identification and characterization of the epithelial polarity receptor ”Frizzled” in Hydra vulgaris
Minobe, S., Fei, K., Yan, L., Sarras, M. P., & Werle, M. J. (2000) · Development Genes and Evolution · doi:10.1007/s004270050312 · Cited by 57
Hayward, D. C., Miller, D. J., & Ball, E. E. (2004) · Development Genes and Evolution · doi:10.1007/s00427-004-0398-0 · Cited by 50
Holland, L. Z., Abi‐Rached, L., Tamme, R., Holland, N. D., Inoko, H., Shiina, T., Burgtorf, C., & Lardelli, M. T. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0160 · Cited by 49
Identification of a Hydra homologue of the β-catenin/plakoglobin/armadillo gene family
Hobmayer, E., Hatta, M., Fischer, R., Fujisawa, T., Holstein, T. W., & Sugiyama, T. (1996) · Gene · doi:10.1016/0378-1119(96)00162-x · Cited by 48
Self-citationOnai, T., Sasai, N., Matsui, M., & Sasai, Y. (2004) · Developmental Cell · doi:10.1016/j.devcel.2004.06.004 · Cited by 43
The evolution of multicellularity and early animal genomes
Brooke, N. M., & Holland, P. W. (2003) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2003.09.002 · Cited by 41
Glycogen synthase kinase 3 has a proapoptotic function in Hydra gametogenesis
Rentzsch, F., Hobmayer, B., & Holstein, T. W. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.10.007 · Cited by 38
Self-citationTorras, R., Yanze, N., Schmid, V. J., & González‐Crespo, S. (2004) · Evolution & Development · doi:10.1111/j.1525-142x.2004.04044.x · Cited by 38
Expression of developmental genes during early embryogenesis of Hydra
Fröbius, A. C., Genikhovich, G., Kürn, U., Anton‐Erxleben, F., & Bosch, T. C. G. (2003) · Development Genes and Evolution · doi:10.1007/s00427-003-0344-6 · Cited by 35
Müller, W. A., Teo, R., & Möhrlen, F. (2004) · The International Journal of Developmental Biology · doi:10.1387/ijdb.15005569 · Cited by 29
A WNTer wonderland in Snowbird
He, X., & Axelrod, J. D. (2006) · Development · doi:10.1242/dev.02452 · Cited by 22
Torras, R., & González‐Crespo, S. (2005) · The International Journal of Developmental Biology · doi:10.1387/ijdb.051980rt · Cited by 20
Axis Formation— β-Catenin Catches a Wnt
Jessen, J. R., & Solnica‐Krezel, L. (2005) · Cell · doi:10.1016/j.cell.2005.03.005 · Cited by 14
The Ups and Downs of a Sea Anemone
Holland, P. W. H. (2004) · Science · doi:10.1126/science.1099829 · Cited by 12
Trembley’s polyps go transgenic
Steele, R. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601983103 · Cited by 12
von Laue, C. C. (2004) · Cited by 2
Research works printed but not linked: 2
- Kirschner MW, Gerhart JC . (2005). The Plausibility of Life. Yale University Press: New Haven, London.
- Miller JR . (2002). The Wnts. Genome Biol 3: reviews3001.1–3001.15.
Cited by
Sorted by citations
Towards an integrated view of Wnt signaling in development
van Amerongen, R., & Nusse, R. (2009) · Development · doi:10.1242/dev.033910 · Cited by 1,213
“Notably, a remarkably diverse Wnt repertoire is already present in Cnidarians, an ancient metazoan phylum that includes fresh water polyps and sea anemones (Guder et al., 2006).”
BackgroundFrizzled and LRP5/6 Receptors for Wnt/ -Catenin SignalingPreprint
MacDonald, B. T., & He, X. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a007880 · Cited by 640
“All of the above “core” Wnt/b-catenin signaling components are present in vertebrates and the well-studied fruit fly Drosophila and are also encoded in sequenced genomes of radial symmetric Cnidarians Hydra magnipapillata and Nematostella vectensis (Guder et al. 2006) and of the primitive metazoan sponge Amphimedon qu…”
BackgroundComparative Aspects of Animal Regeneration
Brockes, J. P., & Kumar, A. (2008) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.24.110707.175336 · Cited by 491
Apoptotic Cells Provide an Unexpected Source of Wnt3 Signaling to Drive Hydra Head Regeneration
Chera, S., Ghila, L., Dobretz, K., Wenger, Y., Bauer, C. R., Buzgariu, W., Martinou, J., & Galliot, B. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.07.014 · Cited by 424
“…Previous work showed the upregulation of Wnt3 expression several hours after mid-gastric section in endodermal epithelial cells (Hobmayer et al., 2000; Guder et al., 2006a), whereas this work identified an immediate and transient overproduction of Wnt3 protein by cells of the interstitial lineage.”
BackgroundResultInfluentialSclerostin and Dickkopf-1 as Therapeutic Targets in Bone Diseases
Ke, H. Z., Richards, W. G., Li, X., & Ominsky, M. S. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1060 · Cited by 409
Metadata
- Authors
- Guder, C., Philipp, I., Lengfeld, T., Watanabe, H., Hobmayer, B., & Holstein, T. W.
- Affiliations
- Heidelberg University (DE)
- Universität Innsbruck (AT)
- Corresponding author
- Holstein, T W
- Venue
- Oncogene
- Published
- 2006-12-04
- Volume
- 25
- Issue
- 57
- Pages
- 7450-7460
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W1983253019
- Cited by
- 177
- References
- 80
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 8 · 2020: 1 · 2019: 11 · 2018: 9 · 2017: 6 · 2016: 11 · 2015: 8 · 2014: 15 · 2013: 7 · 2012: 14
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Marine Invertebrate Physiology and Ecology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Keywords
- Wnt signaling, Cnidaria, Nematostella vectensis, Hydra, regeneration, embryonic development, oral-aboral axis, Hox code, body plan evolution, gene family expansion
- MeSH terms
- Animals, Cnidaria, Hydra, Ligands, Models, Biological, Phylogeny, Sea Anemones, Signal Transduction, Evolution, Molecular, Body Patterning, Wnt Proteins, beta Catenin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review