The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice
Abstract
Recent work has identified LDL receptor-related family members, Lrp5 and Lrp6, as co-receptors for the transduction of Wnt signals. Our analysis of mice carrying mutations in both Lrp5 and Lrp6 demonstrates that the functions of these genes are redundant and are essential for gastrulation. Lrp5;Lrp6 double homozygous mutants fail to establish a primitive streak, although the anterior visceral endoderm and anterior epiblast fates are specified. Thus, Lrp5 and Lrp6 are required for posterior patterning of the epiblast, consistent with a role in transducing Wnt signals in the early embryo. Interestingly, Lrp5+/-;Lrp6-/- embryos die shortly after gastrulation and exhibit an accumulation of cells at the primitive streak and a selective loss of paraxial mesoderm. A similar phenotype is observed in Fgf8 and Fgfr1 mutant embryos and provides genetic evidence in support of a molecular link between the Fgf and Wnt signaling pathways in patterning nascent mesoderm. Lrp5+/-;Lrp6-/- embryos also display an expansion of anterior primitive streak derivatives and anterior neurectoderm that correlates with increased Nodal expression in these embryos. The effect of reducing, but not eliminating, Wnt signaling in Lrp5+/-;Lrp6-/- mutant embryos provides important insight into the interplay between Wnt, Fgf and Nodal signals in patterning the early mouse embryo.
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Cites
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Kremen proteins are Dickkopf receptors that regulate Wnt/β-catenin signalling
Mao, B., Wu, W., Davidson, G., Marhold, J., Li, M., Mechler, B. M., Delius, H., Hoppe, D., Stannek, P., Walter, C., et al. (2002) · Nature · doi:10.1038/nature756 · Cited by 1,038
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“The mechanism by which Wnt signals are transduced through Lrp5/6 appears to involve binding of Lrp5/6 to axin, a downstream negative regulator of the pathway that controls degradation of β-catenin (Mao et al., 2001b; Liu et al., 2003; Tolwinski et al., 2003; Tamai et al., 2004).”
BackgroundRequirement for LIml in head-organizer function
Shawlot, W., & Behringer, R. R. (1995) · Nature · doi:10.1038/374425a0 · Cited by 805
Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow
Bafico, A., Liu, G., Yaniv, A., Gazit, A., & Aaronson, S. A. (2001) · Nature Cell Biology · doi:10.1038/35083081 · Cited by 772
Ang, S.-L., Wierda, A., Wong, D., Stevens, K. A., Cascio, S., Rossant, J., & Zaret, K. S. (1993) · Development · doi:10.1242/dev.119.4.1301 · Cited by 618 · cited 1×
“4A) (Ang et al., 1993; Monaghan et al., 1993; Sasaki and Hogan, 1993), in mutant embryos (Fig.”
Thomas, P. Q., Brown, A., & Beddington, R. S. P. (1998) · Development · doi:10.1242/dev.125.1.85 · Cited by 528
Wg/Wnt Signal Can Be Transmitted through Arrow/LRP5,6 and Axin Independently of Zw3/Gsk3β Activity
Tolwinski, N. S., Wehrli, M., Rives, A., Erdeniz, N., DiNardo, S., & Wieschaus, E. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00063-7 · Cited by 286 · cited 1×
“The mechanism by which Wnt signals are transduced through Lrp5/6 appears to involve binding of Lrp5/6 to axin, a downstream negative regulator of the pathway that controls degradation of β-catenin (Mao et al., 2001b; Liu et al., 2003; Tolwinski et al., 2003; Tamai et al., 2004).”
BackgroundHeads or tails: Wnts and anterior–posterior patterning
Yamaguchi, T. P. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00417-1 · Cited by 276
Mesd Encodes an LRP5/6 Chaperone Essential for Specification of Mouse Embryonic Polarity
Hsieh, J.-C., Lee, L., Zhang, L., Wefer, S., Brown, K., DeRossi, C., Wines, M. E., Rosenquist, T., & Holdener, B. C. (2003) · Cell · doi:10.1016/s0092-8674(03)00045-x · Cited by 237
Cited by
Efficient differentiation of human embryonic stem cells to definitive endoderm
D'Amour, K. A., Agulnick, A. D., Eliazer, S., Kelly, O. G., Kroon, E., & Baetge, E. E. (2005) · Nature Biotechnology · doi:10.1038/nbt1163 · Cited by 1,730
Self-citationLDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling:Arrows point the way
He, X., Semenov, M., Tamai, K., & Zeng, X. (2004) · Development · doi:10.1242/dev.01117 · Cited by 1,044
Function and biological roles of the Dickkopf family of Wnt modulators
Niehrs, C. (2006) · Oncogene · doi:10.1038/sj.onc.1210054 · Cited by 995
Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo
Arnold, S. J., & Robertson, E. J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2618 · Cited by 816
Secreted and transmembrane wnt inhibitors and activators
Cruciat, C.-M., & Niehrs, C. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a015081 · Cited by 646
Metadata
- Authors
- Kelly, O. G., Pinson, K. I., & Skarnes, W. C.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2004-06-15
- Volume
- 131
- Issue
- 12
- Pages
- 2803-2815
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2024704592
- Cited by
- 290
- References
- 10
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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