ArticleHuman molecular genetics2015
L-leucine partially rescues translational and developmental defects associated with zebrafish models of Cornelia de Lange syndrome.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Protein turnover downstream of the Nipbl/CRL4 axis contributes to abnormal development in zebrafish embryos.Developmental dynamics : an official publication of the American Association of Anatomists · 2026Article
- Increased interferon I signaling, DNA damage response and evidence of T-cell exhaustion in a patient with combined interferonopathy (Aicardi-Goutières Syndrome, AGS) and cohesinopathy (Cornelia de Lange Syndrome, CdLS).Pediatric rheumatology online journal · 2025Article
- Advancing the Clinical and Molecular Understanding of Cornelia de Lange Syndrome: A Multidisciplinary Pediatric Case Series and Review of the Literature.Journal of clinical medicine · 2024Review
- Cohesin: an emerging master regulator at the heart of cardiac development.Molecular biology of the cell · 2023Article
- Riboceine Rescues Auranofin-Induced Craniofacial Defects in Zebrafish.Antioxidants (Basel, Switzerland) · 2021Article
- Review
- 5q35 duplication presents with psychiatric and undergrowth phenotypes mediated by NSD1 overexpression and mTOR signaling downregulation.Human genetics · 2021Article
- Lithium as a possible therapeutic strategy for Cornelia de Lange syndrome.Cell death discovery · 2021Article
- Zebrafish Models for Human Skeletal Disorders.Frontiers in genetics · 2021Review
- IRX3/5 regulate mitotic chromatid segregation and limb bud shape.Development (Cambridge, England) · 2020Article
- Cornelia de Lange syndrome: from molecular diagnosis to therapeutic approach.Journal of medical genetics · 2020Review
- Non-redundant roles in sister chromatid cohesion of the DNA helicase DDX11 and the SMC3 acetyl transferases ESCO1 and ESCO2.PloS one · 2020Article
- Ribosomal biogenesis as an emerging target of neurodevelopmental pathologies.Journal of neurochemistry · 2019Review
- Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-CaInternational journal of molecular sciences · 2016Article
- Article
- Six2 Is a Coordinator of LiCl-Induced Cell Proliferation and Apoptosis.International journal of molecular sciences · 2016Article
- Non-Invasive Methods to Monitor Mechanisms of Resistance to Tyrosine Kinase Inhibitors in Non-Small-Cell Lung Cancer: Where Do We Stand?International journal of molecular sciences · 2016Review
- The CLC-2 Chloride Channel Modulates ECM Synthesis, Differentiation, and Migration of Human Conjunctival Fibroblasts via the PI3K/Akt Signaling Pathway.International journal of molecular sciences · 2016Article
- Nucleolar Enrichment of Brain Proteins with Critical Roles in Human Neurodevelopment.Molecular & cellular proteomics : MCP · 2016Article
- Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.Scientific reports · 2016Article
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Cohesinopathies are human genetic disorders that include Cornelia de Lange syndrome (CdLS) and Roberts syndrome (RBS) and are characterized by defects in limb and craniofacial development as well as mental retardation. The developmental phenotypes of CdLS and other cohesinopathies suggest that mutations in the structure and regulation of the cohesin complex during embryogenesis interfere with gene regulation. In a previous project, we showed that RBS was associated with highly fragmented nucleoli and defects in both ribosome biogenesis and protein translation. l-leucine stimulation of the mTOR pathway partially rescued translation in human RBS cells and development in zebrafish models of RBS. In this study, we investigate protein translation in zebrafish models of CdLS. Our results show that phosphorylation of RPS6 as well as 4E-binding protein 1 (4EBP1) was reduced in nipbla/b, rad21 and smc3-morphant embryos, a pattern indicating reduced translation. Moreover, protein biosynthesis and rRNA production were decreased in the cohesin morphant embryo cells. l-leucine partly rescued protein synthesis and rRNA production in the cohesin morphants and partially restored phosphorylation of RPS6 and 4EBP1. Concomitantly, l-leucine treatment partially improved cohesinopathy embryo development including the formation of craniofacial cartilage. Interestingly, we observed that alpha-ketoisocaproate (α-KIC), which is a keto derivative of leucine, also partially rescued the development of rad21 and nipbla/b morphants by boosting mTOR-dependent translation. In summary, our results suggest that cohesinopathies are caused in part by defective protein synthesis, and stimulation of the mTOR pathway through l-leucine or its metabolite α-KIC can partially rescue development in zebrafish models for CdLS.
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