IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
A gene of the RNA metabolism is involved in craniofacial morphogenesis.
Autor/es:
ARMAS, P; MARGARIT, E; ALVIZI, L; PASSOS-BUENO, M.R.; CALCATERRA NB
Reunión:
Simposio; Latin American zebrafish network Symposium; 2014
Institución organizadora:
LAZEN
Resumen:
Richieri-Costa-Pereira síndrome (RCPS) is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies. Exome analyses identified an expansión in the 5?UTR of EIF4A3 gene, which codes for the main helicaseof the exón-junction complex (EJC). RCPS patiens shoed lower abundance of mRNA encoding EIF4A3 than healthy individuals, both in White-blood cells and mesenchimal cells. In this work the RCPS was modelled in zebrafish by using three morpholino (MO) designed to specifically reduce the expression of the gene eif4a3. MOs were injected in 2-4 cell staged embryos and phenotipes were assesed at 24 hours post-fertilization. Morphants displayed craniofacial abnormalities comparable to those one observed in RCPS patiens whitout significant changes in the rest of the body. Phenotypes were almost fully rescued by the injection of a synthetic mRNA coding for the chimera eif4a3-eGFP. RT-qPCR performed using RNA prepared from controls and morphant embryos showed significant variations in the expression of neural crest gene markers. These data demostrated that RCPS is caused by a deficiency of EIF4A3. We further show for the first time a gene involved in the metabolism of RNA participates in craniofacial morphogenesis and that this function is conserved in vertebrates.