ArticleNature2017
Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
232 citing papers in PubMed, 414 citations in OpenAlex.
- Architecture of the Norrin signaling complex and structure-guided surrogate design.Nature structural & molecular biology · 2026Article
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Building and regenerating intestines by manipulating intestinal stem cells.Nature reviews. Gastroenterology & hepatology · 2026Review
- Mitophagy and Noncoding RNA Regulation in Type 2 Diabetes Mellitus: Molecular Mechanisms, Tissue-Specific Evidence and Translational Perspective.Biomedicines · 2026Review
- Rasgrp1-Mediated Dampening of EGFR Signals Supports Coordinated Mammary Gland Development.Cells · 2026Article
- Beyond the target: implications of Wnt pathway inhibitors on bone health.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Lipopolysaccharide promotes rheumatoid arthritis by enhancing Wnt7b mediated macrophage-FLS communication.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- A dual-pathway Wnt-IL-13 fusion protein enhances human intestinal regeneration through tuft cell activation.The Journal of biological chemistry · 2026Article
- The Canonical Wnt Surrogate Agonist scFv-Dkk1c Ameliorates Spinal Cord Injury in Rats.Molecular neurobiology · 2026Article
- MiR-30a-5p mediates epileptogenesis in epilepsy models by targeting SOX4 to regulate the Wnt/β-catenin pathway.Epilepsia open · 2026Article
- Targeting frizzleds with small-molecule compounds-back to square one or light at the end of the tunnel?The Journal of biological chemistry · 2026Review
- Peptide RL-QN15 Regulates Functions of Epidermal Stem Cells to Accelerate Skin Wound Regeneration via the FZD8/β-Catenin Axis.Exploration (Beijing, China) · 2026Article
- A Wnt-induced conformational phospho-switch in DVL3 controls association with Frizzled receptors and Wnt/β-catenin signaling.Science advances · 2026Article
- FTO Controls Endometrial Receptivity and Embryo Implantation through Regulating mCommunications biology · 2026Article
- Eutopic echoes ectopic: organoid-based evidence of shared hormone dysregulation in endometriosis.Reproductive biology and endocrinology : RB&E · 2026Article
- Interpretable machine learning uncovers structural determinants of Wnt-Wntless binding specificity from atomistic simulations.Communications chemistry · 2026Article
- Oxidative stress affects intestinal health by inhibiting the differentiation of porcine intestinal epithelial cells through producing arachidonic acid.Science China. Life sciences · 2026Article
- Peptide-based Wnt signal activation enables scalable production of clinical-grade patient-derived intestinal organoids for regenerative cell therapy.Stem cell research & therapy · 2026Article
- Article
- Long-term feeder cell-free cat intestinal organoid cultures to study Toxoplasma gondii's sexual development.Communications biology · 2026Article
172 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
Abstract
Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors. As a result of their acylation, Wnt proteins are very hydrophobic and require detergents for purification, which presents major obstacles to the preparation and application of recombinant Wnt proteins. This hydrophobicity has hindered the determination of the molecular mechanisms of Wnt signalling activation and the functional importance of FZD subtypes, and the use of Wnt proteins as therapeutic agents. Here we develop surrogate Wnt agonists, water-soluble FZD-LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains. Similar to WNT3A, these Wnt agonists elicit a characteristic β-catenin signalling response in a FZD-selective fashion, enhance the osteogenic lineage commitment of primary mouse and human mesenchymal stem cells, and support the growth of a broad range of primary human organoid cultures. In addition, the surrogates can be systemically expressed and exhibit Wnt activity in vivo in the mouse liver, regulating metabolic liver zonation and promoting hepatocyte proliferation, resulting in hepatomegaly. These surrogates demonstrate that canonical Wnt signalling can be activated by bi-specific ligands that induce receptor heterodimerization. Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.