Artículo
Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes
Porcel de Peralta, Mauro Sebastián
; Mouguelar, Valeria Soraya
; Sdrigotti, María Antonela
; Ishiy, Felipe A. A.; Fanganiello, Roberto D.; Passos Bueno, Maria R.; Coux, Gabriela
; Calcaterra, Nora Beatriz
Fecha de publicación:
10/2016
Editorial:
Nature Publishing Group
Revista:
Cell Death and Disease
ISSN:
2041-4889
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Treacher 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 ROS-cytoprotective 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.
Palabras clave:
Treacher Collins
,
Cnbp
,
Estrés Oxidativo
,
Treacle
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IBR)
Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Citación
Porcel de Peralta, Mauro Sebastián; Mouguelar, Valeria Soraya; Sdrigotti, María Antonela; Ishiy, Felipe A. A.; Fanganiello, Roberto D.; et al.; Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes; Nature Publishing Group; Cell Death and Disease; 7; 10; 10-2016; 2397-2397
Compartir
Altmétricas