Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes

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dc.citation.titleCell Death and Disease
dc.citation.volume7
dc.creatorPorcel de Peralta, Mauro S.
dc.creatorMouguelar, Valeria Soraya
dc.creatorSdrigotti, María Antonella
dc.creatorIshiy, Felipe A. A.
dc.creatorFanganiello, Roberto D.
dc.creatorPassos Bueno, Maria R.
dc.creatorCoux, Gabriela
dc.creatorCalcaterra, Nora B.
dc.date.accessioned2024-10-25T15:50:43Z
dc.date.available2024-10-25T15:50:43Z
dc.date.issued2016-10-06
dc.description.abstractTreacher Collins Syndrome (TCS) is a rare congenital disease (1:50 000 live births) characterized by craniofacial defects, including hypoplasia of facial bones, cleft palate and palpebral fissures. Over 90% of the cases are due to mutations in the TCOF1 gene, which codifies the nucleolar protein Treacle. Here we report a novel TCS-like zebrafish model displaying features that fully recapitulate the spectrum of craniofacial abnormalities observed in patients. As it was reported for a Tcof1+/ − mouse model, Treacle depletion in zebrafish caused reduced rRNA transcription, stabilization of Tp53 and increased cell death in the cephalic region. An increase of ROS along with the overexpression of redox-responsive genes was detected; furthermore, treatment with antioxidants ameliorated the phenotypic defects of craniofacial anomalies in TCS-like larvae. On the other hand, Treacle depletion led to a lowering in the abundance of Cnbp, a protein required for proper craniofacial development. Tcof1 knockdown in transgenic zebrafish overexpressing cnbp resulted in barely affected craniofacial cartilage development, reinforcing the notion that Cnbp has a role in the pathogenesis of TCS. The cnbp overexpression rescued the TCS phenotype in a dose-dependent manner by a ROScytoprotective action that prevented the redox-responsive genes’ upregulation but did not normalize the synthesis of rRNAs. Finally, a positive correlation between the expression of CNBP and TCOF1 in mesenchymal cells from both control and TCS subjects was found. Based on this, we suggest CNBP as an additional target for new alternative therapeutic treatments to reduce craniofacial defects not only in TCS but also in other neurocristopathies.
dc.description.filFil: Porcel de Peralta, Mauro S. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Mouguelar, Valeria Soraya. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Sdrigotti, María Antonella. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Ishiy, Felipe A. A. Universidade de São Paulo. Instituto de Biociencias. Departmento de Genetica e Biologia Evolutiva; Brazil.
dc.description.filFil: Fanganiello, Roberto D. Universidade de São Paulo. Instituto de Biociencias. Departmento de Genetica e Biologia Evolutiva; Brazil.
dc.description.filFil: Passos Bueno, Maria R. Universidade de São Paulo. Instituto de Biociencias. Departmento de Genetica e Biologia Evolutiva; Brazil.
dc.description.filFil: Coux, Gabriela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.filFil: Calcaterra, Nora B. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR-CONICET); Argentina.
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT 2014-1885
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PIP 00773
dc.format.extent1-14
dc.identifier.issn2041-4889
dc.identifier.urihttps://hdl.handle.net/2133/27986
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.publisherversionhttps://www.nature.com/articles/cddis2016299
dc.relation.publisherversionhttps://doi.org/10.1038/cddis.2016.299
dc.rightsopenAccess
dc.rights.holderPorcel de Peralta, Mauro S.
dc.rights.holderMouguelar, Valeria Soraya
dc.rights.holderSdrigotti, María Antonella
dc.rights.holderIshiy, Felipe A. A.
dc.rights.holderFanganiello, Roberto D.
dc.rights.holderPassos Bueno, Maria R.
dc.rights.holderCoux, Gabriela
dc.rights.holderCalcaterra, Nora B.
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCraniofacial abnormalities
dc.subjectFacial bones
dc.subjectMandibulofacial dysostosis
dc.subjectOxidation-reduction
dc.titleCnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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