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Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann's organizer
Abstract
An abundant cDNA enriched in Spemann's organizer, cerberus, was isolated by differential screening. It encodes a secreted protein that is expressed in the anterior endomesoderm. Microinjection of cerberus mRNA into Xenopus embryos induces ectopic heads, and duplicated hearts and livers. The results suggest a role for a molecule expressed in the anterior endoderm in the induction of head structures in the vertebrate embryo.
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“In the extra-cellular matrix, a number of secreted proteins that bind to Wnts and prevent their interaction with either Fz or LRP5/6 to antagonize Wnt signaling have been identified. These include Dickkopf (Dkk) proteins,16 Wnt-inhibitor protein (WIF),17 soluble Frizzled-related proteins (SFRP),18 Cerebrus,19 Frzb20 and the context dependent Wnt inhibitor Wise.21”
From Wnt signal transduction pathways (2008) · cites this paper as [19]
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BackgroundSelf-citationXnr2 and Xnr5 unprocessed proteins inhibit Wnt signaling upstream of dishevelled
Onuma, Y., Takahashi, S., Haramoto, Y., Tanegashima, K., Yokota, C., Whitman, M., & Asashima, M. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20574 · Cited by 18
“…used have been previously described: neural cell adhesion molecule (NCAM) and Xwnt8 are in Xenbase (http://www.xenbase.org/ index.html); cerberus (Bouwmeester et al., 1996); dickkopf1 (dkk1) (Glinka et al., 1998); EF-1 and ms-actin (Takahashi et al., 1998); Frzb1 (Agius et al., 2000); msx1…”
MethodSpörle, R., & Schughart, K. (1997) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(97)80078-0 · Cited by 18
Asashima, M., Michiue, T., & Kurisaki, A. (2008) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2008.00990.x · Cited by 17
“In molecular analyses conducted in the 1990s, the head organizer was shown to require several factors, such as Cerberus, frzb, and Dickkopf, for head-inducing activity (Bouwmeester et al. 1996; Leyns et al. 1997; Wang et al. 1997; Glinka et al. 1998).”
Bone Morphogenic Protein: An Elixir for Bone Grafting—A Review
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“TAB1 (Tak binding protein) is able to bind to p38-a and is activated by autophosphorylation.(77) TAK1 (transforming growth factor b–activated kinase 1) is a Map kinase kinase and is activated by BMP-4 and BMP-2 stimulation.”
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“The Genebank accession number of Xgl is AF308810. histology were done as described (Bouwmeester et al., 1996).”
Self-citationGenomic profiling of Mixer and Sox17β targets during Xenopus endoderm development
Dickinson, K., Leonard, J., & Baker, J. C. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20636 · Cited by 17
“The endoderm is also a source of instructive cues, providing developmental signals to structures in the embryo such as the head and heart (Nascone and Mercola, 1995; Bouwmeester et al., 1996; Beddington and Robertson, 1998; Couly et al., 2002).”
BackgroundSchultheiss, T. M., & Lassar, A. B. (1999) · Elsevier eBooks · doi:10.1016/b978-012329860-7/50006-4 · Cited by 17
TGF-β/BMPs: Crucial crossroad in neural autoimmune disorders
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“…(Sasai et al. 1996) and EF1a (Krieg et al. 1989) were analyzed as previously described (Hemmati-Brivanlou & Melton 1994; LaBonne & Whitman 1994; Wilson & Melton 1994; Hatada et al. 1995; Lai et al. 1995; Sasai et al. 1995; Bouwmeester et al. 1996; Sasai et al. 1996; Takahashi et al. 1998).”
MethodGeneration of animal form by the Chordin/Tolloid/ BMP gradient: 100 years after D'Arcy Thompson
Robertis, E. M. D., Moriyama, Y., & Colozza, G. (2017) · Development Growth & Differentiation · doi:10.1111/dgd.12388 · Cited by 15
“1998), and the multiple inhibitor Cerberus (Bouwmeester et al. 1996).”
BackgroundSelf-citationZhang, X., Gao, Y. H., Lü, L., Zhang, Z., Gan, S., Xu, L., Lei, A., & Cao, Y. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.646554 · Cited by 15
“tion of anterior structures (34, 35), and the expression of xag2, a marker gene for the most anterior structure, were reduced significantly in the Jmjd6 morphant, whereas chrd and gsc expression was not changed (Fig.”
BackgroundVitorino, M., Silva, A. C., Inácio, J. M., Ramalho, J. S., Gur, M., Fainsod, A., Steinbeißer, H., & Belo, J. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135504 · Cited by 15
“laevis embryos were performed as previously described [22].”
MethodBMP signal attenuates FGF pathway in anteroposterior neural patterning
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“Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T, de Robertis EM (1999): The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals.”
BackgroundInfluentialChen, Y., Hollemann, T., Pieler, T., & Grunz, H. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00229-4 · Cited by 15
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Opazo, J. C., Hoffmann, F. G., Zavala, K., & Edwards, S. V. (2021) · Developmental Biology · doi:10.1016/j.ydbio.2021.12.002 · Cited by 14
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“…of several Wnt antagonists that are expressed in the anterior ectoderm and the underlying endomesoderm (Glinka et al. 1998; Leyns et al. 1997; Bouwmeester et al. 1996; Bradley et al. 2000; Pera and De Robertis 2000) have indicated that the inhibition of Wnt/β-catenin signaling in the…”
BackgroundEarly Events in Frog Blastomere Fate Determination
Sullivan, S. A., Moore, K. B., & Moody, S. A. (1999) · Elsevier eBooks · doi:10.1016/b978-012505255-9/50021-3 · Cited by 14
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“Since the discovery of the organizer, several screens have been carried out to identify genes involved in dorso-ventral patterning [5-9].”
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Shibata, M., Itoh, M., Ohmori, S., Shinga, J., & Taira, M. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0428 · Cited by 14
“1 Wnt antagonists include Cerberus (Bouwmeester et al., 1996), Dkk-1 (Glinka et al., 1998), and Frzb-1 (Leyns et al., 1997; Wang et al., 1997a), which are expressed mainly in the head organizer region.”
BackgroundMolecular Determinants of Cardiac Development and Congenital Disease
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“Microinjection, in situ hybridizations and RT-PCR were carried out as described (Bouwmeester et al., 1996).”
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“laevis specifies the anterior endoderm by expressing the cerberus gene (Bouwmeester et al. 1996).”
BackgroundInfluentialGene expression and pattern formation during early embryonic development in amphibians
Grunz, H. (1999) · Journal of Biosciences · doi:10.1007/bf02942663 · Cited by 13
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“, 1994), Goosecoid and ODC (Lemaire and Gurdon, 1994), and Cerberus (Bouwmeester et al., 1996) were as previously described.”
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Lee, S. J., Kim, S., Choi, S., & Han, J. (2009) · Mechanisms of Development · doi:10.1016/j.mod.2009.11.001 · Cited by 10
Self-citationTes regulates neural crest migration and axial elongation in Xenopus
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The BMP antagonists cerberus-like and noggin do not interact during mouse forebrain development
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BackgroundInduction of altered gene expression in early embryos
Rogers, M. B., Glozak, M. A., & Heller, L. C. (1997) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(97)00176-0 · Cited by 10
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“5 (Bouwmeester et al., 1996; Belo et al., 1997), and it has been demonstrated that the XCer expressing endoderm is required for heart inducing activity (Schultheiss et al., 1995; Schneider and Mercola, 1999; Marvin et al., 2001).”
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“The single defined extracellular matrix (ECM) of laminin was used alongside the commonly chosen undefined ECM of Matrigel, because laminin is preferential to other ECM proteins for the adhesion and maintenance of pluripotent hESCs [7,13].”
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“However, Bouwmeester et al. (1996) showed that the leading edge tissue is a rather weak inducer of the secondary axis.”
BackgroundLepperdinger, G., Engel, E., & Richter, K. (1997) · Development Genes and Evolution · doi:10.1007/s004270050105 · Cited by 9
“Further data suggests that dorsal values are specified by antagonistic signals emanating from the Spemann organizer (Spemann and Mangold 1924; Chitnis et al. 1995; Sasai et al. 1995; Kelly and Melton 1995; Launay et al. 1996; Bouwmeester et al. 1996 ).”
BackgroundIdentification and expression of XRTN2 and XRTN3 during Xenopus development
Park, E. C., Shim, S., & Han, J. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20327 · Cited by 9
“Ornithine decarboxylase (Bouwmeester et al., 1996) was used as a loading control.”
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Snider, L. D., & Tapscott, S. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.12.5061-5072.2005 · Cited by 9
“DNA templates for probe synthesis were prepared from the following plasmids: XIC (44), NCAM (27), XMyoD (38), goosecoid (8), chordin (40), Xnot (47), En2 (19), Wnt8 (7), Krox20 (3), Xnr3 (43), Vent1 (15), Cerberus ( 2 ), and Xanf (52).”
MethodMaéno, M., Komiyama, K., Matsuzaki, Y., Hosoya, J., Kurihara, S., Sakata, H., & Izutsu, Y. (2012) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2011.01321.x · Cited by 8
“5 in VMZ explants (Bouwmeester et al. 1996), but the same treatment did not induce the expression of mpo (Tashiro et al. 2006).”
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“5A; Bouwmeester et al., 1996; Jones et al., 1999; Schneider and Mercola 1999; de Souza and Niehrs, 2000; Silva et al., 2003).”
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Klingbeil, P., Frazzetto, G., & Bouwmeester, T. (2001) · The International Journal of Developmental Biology · doi:10.1387/ijdb.11330857 · Cited by 8
“Embryo manipulations, in situ hybridization and microinjection RT-PCR analysis, whole mount in situ hybridization, animal cap assays and histology were done as described (Bouwmeester et al., 1996; Fetka et al., 2000).”
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Choi, S., Chang, J.-Y., & Han, J. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5300 · Cited by 8
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“Based on the expression patterns of SMO - inducing molecules (18, 40, 41) and using the SMO fate maps (42, 43), we microinjected the SMO precursor cells of the 32 - cell stage embryo with fluorescent dextran lineage tracers, labeling the dorsal - animal (D112 in green) and the dorsal - vegetal…”
BackgroundMethodZhang, S., Li, J., Lea, R., Amaya, E., & Dorey, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0079469 · Cited by 7
“Cerberus is a secreted protein expressed in the anterior domain of the mesendoderm [30].”
BackgroundWagner, G., Singhal, N., Nicetto, D., Straub, T., Kremmer, E., & Rupp, R. A. W. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006757 · Cited by 7
Krishnapati, L. S., Khade, S., Trimbake, D., Patwardhan, R., Nadimpalli, S. K., & Ghaskadbi, S. (2020) · Developmental Dynamics · doi:10.1002/dvdy.238 · Cited by 6
Miyagi, A., Negishi, T., Yamamoto, T. S., & Ueno, N. (2015) · Developmental Biology · doi:10.1016/j.ydbio.2015.08.001 · Cited by 7
Generation of Hepatocyte-Like Cells from Human Pluripotent Stem Cells
Noto, F. K., & Duncan, S. A. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7696-2_10 · Cited by 7
Miyazaki, A., Ishii, K. K., Yamashita, S., Nejigane, S., Matsukawa, S., Ito, Y., Onuma, Y., Asashima, M., & Michiue, T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046630 · Cited by 7
“Similar inhibition was observed with Xwnt8, mix, mixer, Cerberus (Cer), and Sox17a [23–27] (Fig.”
ResultNakajima, Y., Okamoto, H., & Kubo, T. (2009) · Genes to Cells · doi:10.1111/j.1365-2443.2009.01291.x · Cited by 7
“BMP inhibitors, such as noggin (Smith & Harland 1992), follistatin (Hemmati-Brivanlou et al. 1994), chordin (Sasai et al. 1994) and Cerberus (Bouwmeester et al. 1996), block the BMP-Smad signaling pathway and this affects ectodermal fate to direct differentiation from epidermis to neural tissue.”
BackgroundUncorking gastrulation: the morphogenetic movement of bottle cells
Lee, J.-Y. (2011) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.19 · Cited by 7
Experimental Embryological Methods for Analysis of Neural Induction in the Amphibian
Keller, R. E., Poznanski, A., & Elul, T. (2003) · Humana Press eBooks · doi:10.1385/1-59259-270-8:351 · Cited by 7
Comparison of induction during development between Xenopus tropicalis and Xenopus laevis
Sedohara, A., Suzawa, K., & Asashima, M. (2006) · The International Journal of Developmental Biology · doi:10.1387/ijdb.052021as · Cited by 7
“…the expression of organizer marker genes, such as chordin (chd) and cerberus (cer), whereas lower doses of activin induced the mesodermal marker gene,nXbrachyury (Xbra) in animal cap explants from Xenopus laevis (Bouwmeester et al., 1996, Sasai et al., 1994, Smith, 1993, Smith et al., 1991).”
BackgroundInfluentialAsashima, M., Yokota, C., Takahashi, S., Lau, C. L., & Malacinski, G. M. (1999) · The International Journal of Developmental Biology · doi:10.1387/ijdb.10213077 · Cited by 7
‘Three signals - three body axes’ as patterning principle in bilaterians
Niehrs, C., Zapparoli, E., & Lee, H. (2024) · Cells and Development · doi:10.1016/j.cdev.2024.203944 · Cited by 8
“Certain growth factor antagonists embody signal integration in one molecule, for example, Cerberus secreted from the head organizer inhibits BMP, Nodal and Wnt signaling to induce dorsoanterior mesendoderm (Bouwmeester et al., 1996; Piccolo et al., 1999) (Fig.”
Neural induction: New achievements and prospects
Zaraisky, A. G. (2007) · Molecular Biology · doi:10.1134/s002689330702001x · Cited by 6
“In addition to noggin and chordin, the following BMP-binding factors are involved in neural induction: cerberus [40], Cv2 [41], DAN [42], follistatin [43], gremlin [44], two noggin homologs (noggin2 [45] and noggin4 [46]), tsukushi [47], and fugacin/Xnr3 [48, 49].”
BackgroundDifferentiation: A Central Topic in Developmental and Cell Biology
Müller, W. A. (1999) · Die Naturwissenschaften · doi:10.1007/s001140050655 · Cited by 6
“Cell 89 :681–684 Bouwmeester T, Sung-Hyun K, Sasai Y, Lu B, De Robertis EM (1996) Cerberus is a head-inducing secreted factor expressed in the anterior endoderm of Spemann’s organizer.”
BackgroundThe Molecular Basis of the Gastrula Organizer in Amphibians and Cnidarians
Yasuoka, Y., & Taira, M. (2018) · Diversity and commonality in animals · doi:10.1007/978-4-431-56609-0_31 · Cited by 6
Lee, S.-H., Kim, C., Lee, H.-K., Kim, Y.-K., Ismail, T., Jeong, Y., Park, K., Park, M. J., Park, D., & Lee, H. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.09.051 · Cited by 6
Germ Layer Induction in ESC—Following the Vertebrate Roadmap
Smith, J., Wardle, F. C., Loose, M., Stanley, E. G., & Patient, R. K. (2007) · Current Protocols in Stem Cell Biology · doi:10.1002/9780470151808.sc01d01s1 · Cited by 6
de la Calle‐Mustienes, E., & Gómez-Skármeta, J. L. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00280-4 · Cited by 6
Head organizer: Cerberus and IGF cooperate in brain induction in Xenopus embryos
Azbazdar, Y., Pera, E. M., & Robertis, E. M. D. (2023) · Cells and Development · doi:10.1016/j.cdev.2023.203897 · Cited by 5
Self-citationZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation
Wang, C., Liu, Z., Zeng, Y., Zhou, L., Long, Q., Hassan, I. U., Zhang, Y., Qi, X., Cai, D., Mao, B., et al. (2024) · EMBO Reports · doi:10.1038/s44319-023-00046-w · Cited by 5
“3F), which may explain the defective head formation in the zswim4 morphant (Bouwmeester et al, 1996; Sander et al, 2007).”
Identification and developmental expression of Xenopus hmga2β
Benini, F., Onorati, M., Altamura, S., Manfioletti, G., & Vignali, R. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.074 · Cited by 5
An Intact Brachyury Function Is Necessary to Prevent Spurious Axial Development in Xenopus laevis
Aguirre, C. E., Murgan, S., Carrasco, A. E., & López, S. L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054777 · Cited by 5
“without trunk-tail structures [61] [66].”
BackgroundRepression of Inappropriate Gene Expression in the Vertebrate Embryonic Ectoderm
Reich, S., & Weinstein, D. C. (2019) · Genes · doi:10.3390/genes10110895 · Cited by 6
Yamamoto, T., Kaneshima, T., Tsukano, K., & Michiue, T. (2023) · Developmental Biology · doi:10.1016/j.ydbio.2023.01.011 · Cited by 4
García, C. A. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11055-4 · Cited by 5
Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula
Nagel, M., Barua, D., Damm, E. W., Kashef, J., Hofmann, R., Ershov, A., Cecilia, A., Moosmann, J. P., Baumbach, T., & Winklbauer, R. (2021) · Development · doi:10.1242/dev.198960 · Cited by 5
Metadata
- Authors
- Bouwmeester, T., Kim, S.-H., Sasai, Y., Lu, B., & Robertis, E. M. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Nature
- Published
- 1996-08
- Volume
- 382
- Issue
- 6592
- Pages
- 595-601
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2081939122
- Cited by
- 759
- References
- 44
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 10 · 2017: 13 · 2016: 14 · 2015: 14 · 2014: 10 · 2013: 21 · 2012: 23
- FWCI
- 23.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- Cerberus, Spemann's organizer, anterior endoderm, secreted proteins, head induction, Xenopus embryo, gene expression, embryonic induction
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Blastomeres, Digestive System, Embryonic Induction, Endoderm, Gastrula, Head, Mesoderm, Molecular Sequence Data, Proteins, RNA, Messenger, Tail, Ultraviolet Rays, Xenopus, Cell Polarity, In Situ Hybridization, DNA Primers, DNA, Complementary, Xenopus Proteins, Intercellular Signaling Peptides and Proteins
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