Cited by 321Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene RegulationHedgehog Signaling Pathway Studies

Wise, a context-dependent activator and inhibitor of Wnt signalling

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Itasaki, Nobue, Jones, C. Michael, Mercurio, Sara, Rowe, Alison, Domingos, Pedro M., Smith, James C., Krumlauf, Robb·2003·Development

Abstract

We have isolated a novel secreted molecule, Wise, by a functional screen for activities that alter the anteroposterior character of neuralised Xenopus animal caps. Wise encodes a secreted protein capable of inducing posterior neural markers at a distance. Phenotypes arising from ectopic expression or depletion of Wise resemble those obtained when Wnt signalling is altered. In animal cap assays, posterior neural markers can be induced by Wnt family members, and induction of these markers by Wise requires components of the canonical Wnt pathway. This indicates that in this context Wise activates the Wnt signalling cascade by mimicking some of the effects of Wnt ligands. Activation of the pathway was further confirmed by nuclear accumulation of β-catenin driven by Wise. By contrast, in an assay for secondary axis induction, extracellularly Wise antagonises the axis-inducing ability of Wnt8. Thus, Wise can activate or inhibit Wnt signalling in a context-dependent manner. The Wise protein physically interacts with the Wnt co-receptor,lipoprotein receptor-related protein 6 (LRP6), and is able to compete with Wnt8 for binding to LRP6. These activities of Wise provide a new mechanism for integrating inputs through the Wnt coreceptor complex to modulate the balance of Wnt signalling.

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Crossref · 10.1242/dev.00674

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Authors
Itasaki, N., Jones, C. M., Mercurio, S., Rowe, A., Domingos, P. M., Smith, J. C., & Krumlauf, R.
Affiliations
National Institute for Medical Research (GB)
Venue
Development
Published
2003-09-15
Volume
130
Issue
18
Pages
4295-4305
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2095537830
Cited by
321
References
72
Citations by year
2026: 1 · 2025: 3 · 2024: 1 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 14 · 2019: 8 · 2018: 10 · 2017: 14 · 2016: 14 · 2015: 10 · 2014: 14 · 2013: 20 · 2012: 20
FWCI
6.66
Type
journal article
Language
en
Licence
other-oa
Locations
  • Development (publishedVersion)
  • PubMed (publishedVersion)
  • Explore Bristol Research (publishedVersion, other-oa)
  • Bristol Research (University of Bristol) (submittedVersion, other-oa)
  • BOA (University of Milano-Bicocca) (submittedVersion)
Funders
Medical Research Council
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 › Hedgehog Signaling Pathway Studies
Keywords
WISE, Wnt signaling, canonical Wnt pathway, LRP6, Wnt8, β-catenin nuclear accumulation, secreted proteins, anterior-posterior patterning, neural induction
MeSH terms
Noggin Protein, Amino Acid Sequence, Animals, Carrier Proteins, Cytoskeletal Proteins, Embryonic Induction, Humans, Molecular Sequence Data, Morphogenesis, Phenotype, Proteins, Proto-Oncogene Proteins, Receptors, LDL, Xenopus laevis, Signal Transduction, Biomarkers, Trans-Activators, Oligonucleotides, Antisense, Sequence Alignment, Cell Polarity, In Situ Hybridization, Activins, Xenopus Proteins, Zebrafish Proteins, Wnt Proteins, beta Catenin, Low Density Lipoprotein Receptor-Related Protein-6

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