ArticleHuman molecular genetics2016
Irf6 directly regulates Klf17 in zebrafish periderm and Klf4 in murine oral epithelium, and dominant-negative KLF4 variants are present in patients with cleft lip and palate.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 58 citations in OpenAlex.
- Systems-level analysis identifies IRF6 as an inhibitor of epithelial-mesenchymal transition.Journal of biological engineering · 2026Article
- Article
- Functional Validation of Noncoding Variants Associated With Nonsyndromic Orofacial Cleft.Human mutation · 2025Review
- Dissecting the regulatory logic of specification and differentiation during vertebrate embryogenesis.bioRxiv : the preprint server for biology · 2024Article
- Periderm Fate during Palatogenesis: TGF-β and Periderm Dedifferentiation.Journal of dental research · 2023Article
- Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?medRxiv : the preprint server for health sciences · 2023Article
- Revisiting the embryogenesis of lip and palate development.Oral diseases · 2022Review
- NELL-1 in Genome-Wide Association Studies across Human Diseases.The American journal of pathology · 2022Review
- Aging disrupts circadian gene regulation and function in macrophages.Nature immunology · 2022Article
- Zebrafish as model for studies in dentistry.Journal of orthodontic science · 2022Review
- Consistent downregulation of the cleft lip/palate-associated genesFrontiers in oncology · 2022Article
- Lack of IRF6 Disrupts Human Epithelial Homeostasis by Altering Colony Morphology, Migration Pattern, and Differentiation Potential of Keratinocytes.Frontiers in cell and developmental biology · 2021Article
- AnDevelopment (Cambridge, England) · 2020Article
- Inactivation ofDisease models & mechanisms · 2020Article
- Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near humaneLife · 2020Article
- PBX-WNT-P63-IRF6 pathway in nonsyndromic cleft lip and palate.Birth defects research · 2020Article
- A Novel Van der Woude Syndrome-CausingFrontiers in cell and developmental biology · 2020Article
- Tissue-Specific Transcriptomes Reveal Gene Expression Trajectories in Two Maturing Skin Epithelial Layers in Zebrafish Embryos.G3 (Bethesda, Md.) · 2019Article
- The RIPK4-IRF6 signalling axis safeguards epidermal differentiation and barrier function.Nature · 2019Article
- Identification of regulatory elements recapitulating early expression of L-plastin in the zebrafish enveloping layer and embryonic periderm.Gene expression patterns : GEP · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Non-syndromic (NS) cleft lip with or without cleft palate (CL/P) is a common disorder with a strong genetic underpinning. Genome-wide association studies have detected common variants associated with this disorder, but a large portion of the genetic risk for NSCL/P is conferred by unidentified rare sequence variants. Mutations in IRF6 (Interferon Regulatory Factor 6) and GRHL3 (Grainyhead-like 3) cause Van der Woude syndrome, which includes CL/P. Both genes encode members of a regulatory network governing periderm differentiation in model organisms. Here, we report that Krüppel-like factor 17 (Klf17), like Grhl3, acts downstream of Irf6 in this network in zebrafish periderm. Although Klf17 expression is absent from mammalian oral epithelium, a close homologue, Klf4, is expressed in this tissue and is required for the differentiation of epidermis. Chromosome configuration capture and reporter assays indicated that IRF6 directly regulates an oral-epithelium enhancer of KLF4. To test whether rare missense variants of KLF4 contribute risk for NSCL/P, we sequenced KLF4 in approximately 1000 NSCL/P cases and 300 controls. By one statistical test, missense variants of KLF4 as a group were enriched in cases versus controls. Moreover, two patient-derived KLF4 variants disrupted periderm differentiation upon forced expression in zebrafish embryos, suggesting that they have dominant-negative effect. These results indicate that rare NSCL/P risk variants can be found in members of the gene regulatory network governing periderm differentiation.
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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.