Lrp6 is required for convergent extension during Xenopus gastrulation
Open accessAbstract
Wnt signaling regulates β-catenin-mediated gene transcription and planar cell polarity (PCP). The Wnt co-receptor, Lrp6, is required for signaling along the β-catenin arm. We show that Lrp6 downregulation (by morpholino injection) or overexpression in Xenopus embryos disrupts convergent extension, a hallmark feature of Wnt/PCP components. In embryos with decreased Lrp6 levels, cells of the dorsal marginal zone (DMZ), which undergoes extensive cellular rearrangements during gastrulation, exhibit decreased length:width ratios, decreased migration, and increased numbers of transient cytoplasmic protrusions. We show that Lrp6 opposes Wnt11 activity and localizes to the posterior edge of migrating DMZ cells and that Lrp6 downregulation enhances cortical and nuclear localization of Dsh and phospho-JNK, respectively. Taken together, these data suggest that Lrp6 inhibits Wnt/PCP signaling. Finally, we identify the region of the Lrp6 protein with Wnt/PCP activity to a stretch of 36 amino acids, distinct from regions required for Wnt/β-catenin signaling. We propose a model in which Lrp6 plays a critical role in the switch from Wnt/PCP to Wnt/β-catenin signaling.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
LRP6 can regulate convergent extension movements.
“However, a recent study has shown that LRP6 can regulate convergent extension movements76 and more studies to address this question will be required.”
From Wnt signal transduction pathways (2008) · cites this paper as [76]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568 · 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
Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction
Glinka, A., Wu, W., Delius, H., Monaghan, A. P., Blumenstock, C., & Niehrs, C. (1998) · Nature · doi:10.1038/34848 · Cited by 1,608 · see citing works
LDL-receptor-related proteins in Wnt signal transduction
Tamai, K., Semënov, M. V., Kato, Y., Spokony, R. F., Liu, C., Katsuyama, Y., Hess, F. J., Saint‐Jeannet, J., & He, X. (2000) · Nature · doi:10.1038/35035117 · Cited by 1,334 · see citing works
arrow encodes an LDL-receptor-related protein essential for Wingless signalling
Wehrli, M., Dougan, S. T., Caldwell, K. A., O’Keefe, L. V., Schwartz, S. L., Vaizel-Ohayon, D., Schejter, E. D., Tomlinson, A., & DiNardo, S. (2000) · Nature · doi:10.1038/35035110 · Cited by 871 · see citing works
A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation
Zeng, X., Tamai, K., Doble, B. W., Li, S., Huang, H., Habas, R., Okamura, H., Woodgett, J. R., & He, X. (2005) · Nature · doi:10.1038/nature04185 · Cited by 849 · see citing works
Habas, R., Kato, Y., & He, X. (2001) · Cell · doi:10.1016/s0092-8674(01)00614-6 · Cited by 842 · see citing works
Simons, M., Gloy, J., Ganner, A., Bullerkotte, A., Bashkurov, M., Krönig, C., Schermer, B., Benzing, T., Cabello, O. A., Jenny, A., et al. (2005) · Nature Genetics · doi:10.1038/ng1552 · Cited by 767 · see citing works
Casein kinase 1 γ couples Wnt receptor activation to cytoplasmic signal transduction
Davidson, G. R., Wu, W., Shen, J., Bilić, J., Fenger, U., Stannek, P., Glinka, A., & Niehrs, C. (2005) · Nature · doi:10.1038/nature04170 · Cited by 581 · see citing works
A Mechanism for Wnt Coreceptor Activation
Tamai, K., Zeng, X., Liu, C., Zhang, X., Harada, Y., Chang, Z., & He, X. (2004) · Molecular Cell · doi:10.1016/s1097-2765(03)00484-2 · Cited by 556 · see citing works
Kao, K. R., & Elinson, R. P. (1988) · Developmental Biology · doi:10.1016/0012-1606(88)90189-3 · Cited by 513 · see citing works
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 · see citing works
How we are shaped: The biomechanics of gastrulation
Keller, R. E., Davidson, L. A., & Shook, D. R. (2003) · Differentiation · doi:10.1046/j.1432-0436.2003.710301.x · Cited by 495 · see citing works
Yamanaka, H., Moriguchi, T., Masuyama, N., Kusakabe, M., Hanafusa, H., Takada, R., Takada, S., & Nishida, E. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf008 · Cited by 454 · see citing works
Casein kinase I transduces Wnt signals
Peters, J. M., McKay, R. M., McKay, J. P., & Graff, J. M. (1999) · Nature · doi:10.1038/43830 · Cited by 447 · see citing works
The hedgehog signaling network
Cohen, M. M. (2003) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20495 · Cited by 418 · see citing works
Analysis of Dishevelled signalling pathways during Xenopus development
Sokol, S. Y. (1996) · Current Biology · doi:10.1016/s0960-9822(96)00750-6 · Cited by 406 · see citing works
Axin and Frat1 interact with Dvl and GSK, bridging Dvl to GSK in Wnt‐mediated regulation of LEF‐1
Li, L., Yuan, H., Weaver, C. D., Mao, J., Farr, G. H., Sussman, D. J., Jonkers, J., Kimelman, D., & Wu, D. (1999) · The EMBO Journal · doi:10.1093/emboj/18.15.4233 · Cited by 403 · see citing works
Planar cell polarity signalling couples cell division and morphogenesis during neurulation
Ciruna, B. G., Jenny, A., Lee, D. W., Mlodzik, M., & Schier, A. F. (2006) · Nature · doi:10.1038/nature04375 · Cited by 400 · see citing works
Xenopus laevis: Practical Uses in Cell and Molecular Biology
(1991) · Methods in cell biology · doi:10.1016/s0091-679x(08)x6010-8 · Cited by 394 · see citing works
The dishevelled protein is modified by wingless signaling in Drosophila.Preprint
Yanagawa, S.-I., van Leeuwen, F. N., Wodarz, A., Klingensmith, J., & Nusse, R. (1995) · Genes & Development · doi:10.1101/gad.9.9.1087 · Cited by 388 · see citing works
Keller, R. E., & Danilchik, M. (1988) · Development · doi:10.1242/dev.103.1.193 · Cited by 378 · see citing works
Cell motility driving mediolateral intercalation in explants of Xenopus laevis
Shih, J., & Keller, R. E. (1992) · Development · doi:10.1242/dev.116.4.901 · Cited by 356 · see citing works
Montcouquiol, M., Sans, N., Huss, D., Kach, J., Dickman, J. D., Forge, A., Rachel, R. A., Copeland, N. G., Jenkins, N. A., Bogani, D., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4680-05.2006 · Cited by 322 · see citing works
Wise, a context-dependent activator and inhibitor of Wnt signalling
Itasaki, N., Jones, C. M., Mercurio, S., Rowe, A., Domingos, P. M., Smith, J. C., & Krumlauf, R. (2003) · Development · doi:10.1242/dev.00674 · Cited by 321 · see citing works
Wang, J., Mark, S., Zhang, X., Qian, D., Yoo, S.-J., Radde‐Gallwitz, K., Zhang, Y., Lin, X., Collazo, A., Wynshaw-Boris, A. J., et al. (2005) · Nature Genetics · doi:10.1038/ng1622 · Cited by 315 · see citing works
PLANAR CELL POLARIZATION: An Emerging Model Points in the Right Direction
Klein, T. J., & Mlodzik, M. (2005) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.012704.132806 · Cited by 311 · see citing works
The planar polarity gene strabismus regulates convergent extension movements in Xenopus
Darken, R. S., Scola, A. M., Rakeman, A. S., Das, G., Mlodzik, M., & Wilson, P. A. (2002) · The EMBO Journal · doi:10.1093/emboj/21.5.976 · Cited by 239 · see citing works
Goto, T., & Keller, R. E. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0673 · Cited by 229 · see citing works
Kühl, M., Geis, K., Sheldahl, L. C., Pukrop, T., Moon, R. T., & Wedlich, D. (2001) · Mechanisms of Development · doi:10.1016/s0925-4773(01)00416-6 · Cited by 219 · see citing works
Wallingford, J. B., & Harland, R. M. (2001) · Development · doi:10.1242/dev.128.13.2581 · Cited by 217 · see citing works
Patterns of cell motility in the organizer and dorsal mesoderm of Xenopus laevis
Shih, J., & Keller, R. E. (1992) · Development · doi:10.1242/dev.116.4.915 · Cited by 214 · see citing works
The prickle-Related Gene in Vertebrates Is Essential for Gastrulation Cell Movements
Takeuchi, M., Nakabayashi, J., Sakaguchi, T. F., Yamamoto, T. S., Takahashi, H., Takeda, H., & Ueno, N. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00245-8 · Cited by 193 · see citing works
Schwarz-Romond, T., Asbrand, C., Bakkers, J., Kühl, M., Schaeffer, H.-J., Huelsken, J., Behrens, J., Hammerschmidt, M., & Birchmeier, W. (2002) · Genes & Development · doi:10.1101/gad.230402 · Cited by 189 · see citing works
Xenopus laevis: Practical uses in cell and molecular biology. Solutions and protocols.
Peng, H. B. (1991) · PubMed · Cited by 176 · see citing works
Gastrulation movements provide an early marker of mesoderm induction in Xenopus laevis
Symes, K., & Smith, J. C. (1987) · Development · doi:10.1242/dev.101.2.339 · Cited by 175 · see citing works
Kinoshita, N., Iioka, H., Miyakoshi, A., & Ueno, N. (2003) · Genes & Development · doi:10.1101/gad.1101303 · Cited by 173 · see citing works
Cell autonomous regulation of multiple Dishevelled-dependent pathways by mammalian Nkd
Yan, D. M., Wallingford, J. B., Sun, T., Nelson, A. M., Sakanaka, C., Reinhard, C., Harland, R. M., Fantl, W. J., & Williams, L. T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.071041898 · Cited by 167 · see citing works
Distinct functions of Rho and Rac are required for convergent extension during Xenopus gastrulation
Tahinci, E., & Symes, K. (2003) · Developmental Biology · doi:10.1016/s0012-1606(03)00206-9 · Cited by 162 · see citing works
Self-citationPlanar cell polarity signaling in vertebrates
Jones, C., & Chen, P. (2007) · BioEssays · doi:10.1002/bies.20526 · Cited by 161 · see citing works
Evidence for kinesin-related proteins in the mitotic apparatus using peptide antibodies
Sawin, K. E., Mitchison, T. J., & Wordeman, L. G. (1992) · Journal of Cell Science · doi:10.1242/jcs.101.2.303 · Cited by 151 · see citing works
Caneparo, L., Huang, Y., Staudt, N. D., Tada, M., Ahrendt, R., Kazanskaya, O., Niehrs, C., & Houart, C. (2007) · Genes & Development · doi:10.1101/gad.406007 · Cited by 150 · see citing works
Directional mesoderm cell migration in the Xenopus gastrula
Winklbauer, R., & Nagel, M. (1991) · Developmental Biology · doi:10.1016/0012-1606(91)90275-8 · Cited by 137 · see citing works
Yokota, C., Kofron, M. J., Zuck, M., Houston, D. W., Isaacs, H. V., Asashima, M., Wylie, C., & Heasman, J. (2003) · Development · doi:10.1242/dev.00434 · Cited by 91 · see citing works
Peng, H. B. (1991) · Cited by 89 · see citing works
Induction of neuronal differentiation by planar signals in Xenopus embryos
Sater, A. K., Steinhardt, R. A., & Keller, R. E. (1993) · Developmental Dynamics · doi:10.1002/aja.1001970405 · Cited by 87 · see citing works
Penzo‐Méndez, A., Umbhauer, M., Djiane, A., Boucaut, J., & Riou, J. (2003) · Developmental Biology · doi:10.1016/s0012-1606(03)00067-8 · Cited by 84 · see citing works
Planar cell polarity genes and neural tube closure
Ueno, N., & Greene, N. D. E. (2003) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.10029 · Cited by 75 · see citing works
Planar cell polarity signaling: a common mechanism for cellular polarization.
Jenny, A., & Mlodzik, M. (2006) · PubMed · Cited by 67 · see citing works
A Library of Monoclonal Antibodies to Torpedo Cholinergic Synaptosomes
Kushner, P. D. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb12799.x · Cited by 66 · see citing works
Lane, M. C., & Keller, R. E. (1997) · Development · doi:10.1242/dev.124.4.895 · Cited by 62 · see citing works
Hyodo‐Miura, J., Yamamoto, T. S., Hyodo, A. C., Iemura, S., Kusakabe, M., Nishida, E., Natsume, T., & Ueno, N. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.04.019 · Cited by 39 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Wnt signal transduction pathways
Komiya, Y., & Habas, R. (2008) · Organogenesis · doi:10.4161/org.4.2.5851 · Cited by 1,528 · see citing works
- Authors
- Tahinci, E., Thorne, C. A., Franklin, J. L., Salic, A., Christian, K. M., Lee, L. A., Coffey, R. J., & Lee, E.
- Affiliations
- Vanderbilt University Medical Center (US)
- Harvard University (US)
- Corresponding author
- Lee, Ethan
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2007-11-15
- Volume
- 134
- Issue
- 22
- Pages
- 4095-4106
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC4428168
- OpenAlex
- W2090723435
- Cited by
- 73
- References
- 52
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 1 · 2014: 4 · 2013: 8 · 2012: 4
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Pew Charitable Trusts
- National Institutes of Health (DK007563)
- U.S. Public Health Service (U01 084239, P50 95103)
- National Cancer Institute (CA46413, P50CA095103, U01CA084239, R01CA046413)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007563)
- Topics
- 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 › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Planarian Biology and Electrostimulation
- Keywords
- LRP6, convergent extension, Xenopus gastrulation, planar cell polarity, Wnt signaling, Wnt11, dorsal marginal zone, DSH, JNK, β-catenin signaling, morpholino knockdown, cell migration
- MeSH terms
- Amino Acid Sequence, Animals, Cells, Cultured, Embryo, Nonmammalian, Humans, Mesoderm, Models, Biological, Molecular Sequence Data, Receptors, LDL, Tissue Distribution, Xenopus, Signal Transduction, Cell Polarity, Sequence Homology, Amino Acid, Gene Expression Regulation, Developmental, Body Patterning, Animals, Genetically Modified, Wnt Proteins, beta Catenin, Gastrulation, Low Density Lipoprotein Receptor-Related Protein-6
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