ArticleThe Journal of clinical investigation2014
Disrupting hedgehog and WNT signaling interactions promotes cleft lip pathogenesis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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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
70 citing papers in PubMed, 125 citations in OpenAlex.
- Effects of Smoothened Agonist Exposure on Murine Craniofacial Development.International dental journal · 2026Article
- Loss of SPECC1L in cranial neural crest cells results in increased hedgehog signaling and frontonasal dysplasia.Frontiers in physiology · 2026Article
- Loss of SPECC1L in cranial neural crest cells results in increased hedgehog signaling and frontonasal dysplasia.bioRxiv : the preprint server for biology · 2025Article
- Facial Clefts and the Trigeminal Nerve: A Narrative Review of the Literature and Clinical Considerations in the Era of Personalized Medicine.Journal of personalized medicine · 2025Review
- The developmental bases of cleft lip and cleft palate: cellular and molecular mechanisms.Anatomy & cell biology · 2025Review
- Functional Annotation of De Novo Variants Found Near GWAS Loci Associated With Cleft Lip With or Without Cleft Palate.Birth defects research · 2025Article
- Expression analysis of genes including Zfhx4 in mice and zebrafish reveals a temporospatial conserved molecular basis underlying craniofacial development.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.International journal of molecular sciences · 2025Review
- Article
- Single-cell transcriptome and chromatin accessibility mapping of upper lip and primary palate fusion.Journal of cellular and molecular medicine · 2024Article
- Investigating oral microbiome profiles in patients with cleft lip and palate compared with the healthy control.BMC oral health · 2024Article
- The presence and distribution of various genes in postnatal CLP-affected palatine tissue.Maxillofacial plastic and reconstructive surgery · 2024Article
- Epithelial-mesenchymal crosstalk: the scriptwriter of craniofacial morphogenesis.Frontiers in cell and developmental biology · 2024Review
- Association betweenGenes · 2023Article
- Gene Regulatory Networks and Signaling Pathways in Palatogenesis and Cleft Palate: A Comprehensive Review.Cells · 2023Review
- Single-cell transcriptomic signatures and gene regulatory networks modulated by Wls in mammalian midline facial formation and clefts.Development (Cambridge, England) · 2022Article
- Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate.Scientific reports · 2022Article
- Revisiting the embryogenesis of lip and palate development.Oral diseases · 2022Review
- Regulatory mechanisms of cytoneme-based morphogen transport.Cellular and molecular life sciences : CMLS · 2022Review
- 16p12.1 Deletion Orthologs are Expressed in Motile Neural Crest Cells and are Important for Regulating Craniofacial Development inFrontiers in genetics · 2022Article
10 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
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Cleft lip, which results from impaired facial process growth and fusion, is one of the most common craniofacial birth defects. Many genes are known to be involved in the etiology of this disorder; however, our understanding of cleft lip pathogenesis remains incomplete. In the present study, we uncovered a role for sonic hedgehog (SHH) signaling during lip fusion. Mice carrying compound mutations in hedgehog acyltransferase (Hhat) and patched1 (Ptch1) exhibited perturbations in the SHH gradient during frontonasal development, which led to hypoplastic nasal process outgrowth, epithelial seam persistence, and cleft lip. Further investigation revealed that enhanced SHH signaling restricts canonical WNT signaling in the lambdoidal region by promoting expression of genes encoding WNT inhibitors. Moreover, reduction of canonical WNT signaling perturbed p63/interferon regulatory factor 6 (p63/IRF6) signaling, resulting in increased proliferation and decreased cell death, which was followed by persistence of the epithelial seam and cleft lip. Consistent with our results, mutations in genes that disrupt SHH and WNT signaling have been identified in both mice and humans with cleft lip. Collectively, our data illustrate that altered SHH signaling contributes to the etiology and pathogenesis of cleft lip through antagonistic interactions with other gene regulatory networks, including the canonical WNT and p63/IRF6 signaling pathways.
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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.