ArticleDevelopment (Cambridge, England)2016
Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland development.
Article in Development (Cambridge, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- From Proteome to miRNome: A Review of Multi-Omics Ocular Allergy Research Using Human Tears.International journal of molecular sciences · 2026Review
- Establishment of Mouse Meibomian Gland Organoids for In Vitro Modeling of Meibomian Gland Dysfunction.Investigative ophthalmology & visual science · 2026Article
- DKK3-LRP1 complex and a chemical inhibitor regulate Aβ clearance in models of Alzheimer's disease.Science advances · 2025Article
- What's the situation with ocular inflammation? A cross-seasonal investigation of proteomic changes in ocular allergy sufferers' tears in Victoria, Australia.Frontiers in immunology · 2024Article
- EDA ligand triggers plasma membrane trafficking of its receptor EDAR via PKA activation and SNAP23-containing complexes.Cell & bioscience · 2023Article
- Structure of the Wnt-Frizzled-LRP6 initiation complex reveals the basis for coreceptor discrimination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Role of Ectodysplasin A on the Ocular Surface Homeostasis.International journal of molecular sciences · 2022Review
- Ectodysplasin A (EDA) Signaling: From Skin Appendage to Multiple Diseases.International journal of molecular sciences · 2022Review
- [Research advances on signaling pathways affecting sweat gland development and their involvement in the reconstitution of sweat adenoid cells in vitro].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
- A literature review on function and regulation mechanism of DKK4.Journal of cellular and molecular medicine · 2021Review
- Dickkopf-4 gene expression is associated with differentiation and lymph node metastasis in colorectal cancer.JGH open : an open access journal of gastroenterology and hepatology · 2019Article
- Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in skin appendage formation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structural and functional analysis of Dickkopf 4 (Dkk4): New insights into Dkk evolution and regulation of Wnt signaling by Dkk and Kremen proteins.The Journal of biological chemistry · 2018Article
- Identification, isolation and characterization of human LGR5-positive colon adenoma cells.Development (Cambridge, England) · 2018Article
- Pathogens in the Meibomian gland and conjunctival sac: microbiome of normal subjects and patients with Meibomian gland dysfunction.Infection and drug resistance · 2018Article
- Dickkopf-4 is frequently overexpressed in epithelial ovarian carcinoma and promotes tumor invasion.BMC cancer · 2017Article
- Meibomian gland development: Where, when and how?Differentiation; research in biological diversityReview
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ development. Dkk1 has been widely studied and acts as a general Wnt inhibitor. However, the molecular function of other Dkks remains largely unknown. Here, we show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4 arrests MG growth at early germ phase, which is similar to that observed in Eda-ablated Tabby mice. Consistent with transient Dkk4 action, intact Dkk4 inhibits MG extension but the cleaved form progressively increases during MG development with a concomitant upswing in Wnt activity. Furthermore, both Dkk4 and its receptor (and Wnt co-receptor) Lrp6 are direct Eda targets during MG induction. In cell and organotypic cultures, Dkk4 inhibition is eliminated by elevation of Lrp6. Also, Lrp6 upregulation restores MG formation in Tabby mice. Thus, the dynamic state of Dkk4 itself and its interaction with Lrp6 modulates Wnt function during MG development, with a novel limitation of Dkk4 action by proteolytic cleavage.
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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.