ArticleDisease models & mechanisms2015
Tfap2a-dependent changes in mouse facial morphology result in clefting that can be ameliorated by a reduction in Fgf8 gene dosage.
Article in Disease models & mechanisms, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Tooth agenesis and orofacial clefting: genetic brothers in arms?Human genetics · 2016Pooled it
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- Adam13 interacts with large protein complexes to regulate histone modification and gene expression.Frontiers in cell and developmental biology · 2026Article
- Fibroblast growth factor 8: Multifaceted role in development and developmental disorder.Genes & diseases · 2025Review
- Quantifying the relationship between cell proliferation and morphology during development of the face.Development (Cambridge, England) · 2025Article
- Embryonic Lethal Phenotyping to Identify Candidate Genes Related with Birth Defects.International journal of molecular sciences · 2024Article
- Identification of Molecular Mechanisms of Ameloblastoma and Drug Repositioning by Integration of Bioinformatics Analysis and Molecular Docking Simulation.Bioinformatics and biology insights · 2024Article
- Zebrafish crocc2 mutants exhibit divergent craniofacial shape, misregulated variability, and aberrant cartilage morphogenesis.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Disruption ofFrontiers in cell and developmental biology · 2023Article
- Allele-specific transcription factor binding in a cellular model of orofacial clefting.Scientific reports · 2022Article
- What's Shape Got to Do With It? Examining the Relationship Between Facial Shape and Orofacial Clefting.Frontiers in genetics · 2022Review
- DNA-based eyelid trait prediction in Chinese Han population.International journal of legal medicine · 2021Article
- A vertebrate adaptive radiation is assembled from an ancient and disjunct spatiotemporal landscape.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Intersection of the Genetic Architectures of Orofacial Clefts and Normal Facial Variation.Frontiers in genetics · 2021Article
- Functional Divergence of Mammalian TFAP2a and TFAP2b Transcription Factors for Bidirectional Sleep Control.Genetics · 2020Article
- Genetics and signaling mechanisms of orofacial clefts.Birth defects research · 2020Review
- Anatomical similarity between the Sost-knockout mouse and sclerosteosis in humans.Anatomical record (Hoboken, N.J. : 2007) · 2020Article
- Cleft lip and cleft palate inDevelopment (Cambridge, England) · 2020Article
- Review
- MicroRNA-124-3p suppresses mouse lip mesenchymal cell proliferation through the regulation of genes associated with cleft lip in the mouse.BMC genomics · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Failure of facial prominence fusion causes cleft lip and palate (CL/P), a common human birth defect. Several potential mechanisms can be envisioned that would result in CL/P, including failure of prominence growth and/or alignment as well as a failure of fusion of the juxtaposed epithelial seams. Here, using geometric morphometrics, we analyzed facial outgrowth and shape change over time in a novel mouse model exhibiting fully penetrant bilateral CL/P. This robust model is based upon mutations in Tfap2a, the gene encoding transcription factor AP-2α, which has been implicated in both syndromic and non-syndromic human CL/P. Our findings indicate that aberrant morphology and subsequent misalignment of the facial prominences underlies the inability of the mutant prominences to fuse. Exencephaly also occured in some of the Tfap2a mutants and we observed additional morphometric differences that indicate an influence of neural tube closure defects on facial shape. Molecular analysis of the CL/P model indicates that Fgf signaling is misregulated in the face, and that reducing Fgf8 gene dosage can attenuate the clefting pathology by generating compensatory changes. Furthermore, mutations in either Tfap2a or Fgf8 increase variance in facial shape, but the combination of these mutations restores variance to normal levels. The alterations in variance provide a potential mechanistic link between clefting and the evolution and diversity of facial morphology. Overall, our findings suggest that CL/P can result from small gene-expression changes that alter the shape of the facial prominences and uncouple their coordinated morphogenesis, which is necessary for normal fusion.
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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.