ArticleEMBO molecular medicine2012
Mutant p63 causes defective expansion of ectodermal progenitor cells and impaired FGF signalling in AEC syndrome.
Article in EMBO molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 83 citations in OpenAlex.
- Preclinical Models of Rare Corneal and Ocular Surface Diseases: a Comprehensive Narrative Review.Ophthalmology and therapy · 2026Review
- p63 in skin homeostasis and disease: molecular mechanisms and therapeutic potentials.Cell death discovery · 2026Review
- Genetic Regulation of Wnt/PCP Components Through Fgf10/Fgfr2/Sox9 Module in Tear Duct Development.Investigative ophthalmology & visual science · 2026Article
- A Novel Model System to Identify Cellular and Molecular Defects Underlying Rare Genetic Disorders.Experimental dermatology · 2026Article
- De Novo Missense Variant in TP63 Gene: Insights on Clinical and Molecular Investigations.The journal of gene medicine · 2025Article
- Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Syndrome-Linked p63 Mutations Disrupt Keratinocyte Proliferation and Survival Through Oxidative Stress and Impaired Slc7a11 Expression.International journal of molecular sciences · 2025Article
- Anthracyclines disaggregate and restore mutant p63 function: a potential therapeutic approach for AEC syndrome.Cell death discovery · 2025Article
- p63: A Master Regulator at the Crossroads Between Development, Senescence, Aging, and Cancer.Cells · 2025Review
- RAF1 deficiency causes a lethal syndrome that underscores RTK signaling during embryogenesis.EMBO molecular medicine · 2023Article
- Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.Current topics in developmental biology · 2022Article
- Isoform-Specific Roles of Mutant p63 in Human Diseases.Cancers · 2021Review
- Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening in Prickle 1 Mutant Mice: Genetic Implications for Tear Duct Genesis.Investigative ophthalmology & visual science · 2020Article
- Genetics and signaling mechanisms of orofacial clefts.Birth defects research · 2020Review
- Disruption of the nectin-afadin complex recapitulates features of the human cleft lip/palate syndrome CLPED1.Development (Cambridge, England) · 2020Article
- Ankyloblepharon-ectodermal Defects-cleft Lip-palate Syndrome Due to a Novel Missense Mutation in the SAM Domain of theBalkan journal of medical genetics : BJMG · 2020Article
- Dynamic mRNA Expression Analysis of the Secondary Palatal Morphogenesis in Miniature Pigs.International journal of molecular sciences · 2019Article
- Keratinocyte Growth Factor (KGF) Modulates Epidermal Progenitor Cell Kinetics through Activation of p63 in Middle Ear Cholesteatoma.Journal of the Association for Research in Otolaryngology : JARO · 2018Article
- Master regulatory role of p63 in epidermal development and disease.Cellular and molecular life sciences : CMLS · 2018Review
- Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Closing the Gap: Mouse Models to Study Adhesion in Secondary Palatogenesis.Journal of dental research · 2017Review
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18 authors at 12 institutions in 6 countries.
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Abstract
Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, which is characterized by cleft palate and severe defects of the skin, is an autosomal dominant disorder caused by mutations in the gene encoding transcription factor p63. Here, we report the generation of a knock-in mouse model for AEC syndrome (p63(+/L514F) ) that recapitulates the human disorder. The AEC mutation exerts a selective dominant-negative function on wild-type p63 by affecting progenitor cell expansion during ectodermal development leading to a defective epidermal stem cell compartment. These phenotypes are associated with impairment of fibroblast growth factor (FGF) signalling resulting from reduced expression of Fgfr2 and Fgfr3, direct p63 target genes. In parallel, a defective stem cell compartment is observed in humans affected by AEC syndrome and in Fgfr2b(-/-) mice. Restoring Fgfr2b expression in p63(+/L514F) epithelial cells by treatment with FGF7 reactivates downstream mitogen-activated protein kinase signalling and cell proliferation. These findings establish a functional link between FGF signalling and p63 in the expansion of epithelial progenitor cells and provide mechanistic insights into the pathogenesis of AEC syndrome.
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