ArticleHuman molecular genetics2009
Kinase-activating and kinase-impaired cardio-facio-cutaneous syndrome alleles have activity during zebrafish development and are sensitive to small molecule inhibitors.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 100 citations in OpenAlex.
- Non-Mammalian Models for Understanding Neurological Defects in RASopathies.Biomedicines · 2024Review
- Assessment of the FRET-based Teen sensor to monitor ERK activation changes preceding morphological defects in a RASopathy zebrafish model and phenotypic rescue by MEK inhibitor.Molecular medicine (Cambridge, Mass.) · 2024Article
- The Cardiofaciocutaneous Syndrome: From Genetics to Prognostic-Therapeutic Implications.Genes · 2023Review
- RAS pathway: The new frontier of brain mosaicism in epilepsy.Neurobiology of disease · 2023Review
- Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.Science advances · 2023Article
- The RASopathies: from pathogenetics to therapeutics.Disease models & mechanisms · 2022Review
- IQ-Switch is a QF-based innocuous, silencing-free, and inducible gene switch system in zebrafish.Communications biology · 2021Article
- SPRED2 loss-of-function causes a recessive Noonan syndrome-like phenotype.American journal of human genetics · 2021Article
- Review
- Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials.Nature reviews. Drug discovery · 2021Review
- Crystal Structure Reveals the Full Ras-Raf Interface and Advances Mechanistic Understanding of Raf Activation.Biomolecules · 2021Article
- A Heterozygous Missense Variant inAnimals : an open access journal from MDPI · 2021Article
- Modeling the developmental origins of pediatric cancer to improve patient outcomes.Disease models & mechanisms · 2021Review
- Regulation of the Small GTPase Ras and Its Relevance to Human Disease.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Prolonged response to treatment based on cell-free DNA analysis and molecular profiling in three patients with metastatic cancer: a case series.Therapeutic advances in medical oncology · 2021Article
- Review
- Swimming toward solutions: Using fish and frogs as models for understanding RASopathies.Birth defects research · 2020Review
- Optimizing photoswitchable MEK.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- A new perspective on fungal metabolites: identification of bioactive compounds from fungi using zebrafish embryogenesis as read-out.Scientific reports · 2019Article
- The impact of RASopathy-associated mutations on CNS development in mice and humans.Molecular brain · 2019Review
Corrections and comments
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Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
Abstract
The Ras/MAPK pathway is critical for human development and plays a central role in the formation and progression of most cancers. Children born with germ-line mutations in BRAF, MEK1 or MEK2 develop cardio-facio-cutaneous (CFC) syndrome, an autosomal dominant syndrome characterized by a distinctive facial appearance, heart defects, skin and hair abnormalities and mental retardation. CFC syndrome mutations in BRAF promote both kinase-activating and kinase-impaired variants. CFC syndrome has a progressive phenotype, and the availability of clinically active inhibitors of the MAPK pathway prompts the important question as to whether such inhibitors might be therapeutically effective in the treatment of CFC syndrome. To study the developmental effects of CFC mutant alleles in vivo, we have expressed a panel of 28 BRAF and MEK alleles in zebrafish embryos to assess the function of human disease alleles and available chemical inhibitors of this pathway. We find that both kinase-activating and kinase-impaired CFC mutant alleles promote the equivalent developmental outcome when expressed during early development and that treatment of CFC-zebrafish embryos with inhibitors of the FGF-MAPK pathway can restore normal early development. Importantly, we find a developmental window in which treatment with a MEK inhibitor can restore the normal early development of the embryo, without the additional, unwanted developmental effects of the drug.
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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.