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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“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).”
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Wnt/β-catenin signaling components and mechanisms in bone formation, homeostasis, and disease
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The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway
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DKK1 Antagonizes Wnt Signaling without Promotion of LRP6 Internalization and Degradation
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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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