IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The primary cilia scaffold protein Arl13b is required during eye morphogenesis.
Autor/es:
ACOSTA, SANDRA; TAKATA, NOZOMU; OLIVER, GUILLERMO; FIORE, LUCIANO; MA, WANSHU
Lugar:
Buenos aires
Reunión:
Congreso; LASDV 2019 meeting; 2019
Institución organizadora:
Latin American Society for Developmental Biology
Resumen:
Cilia defects can impact essential signaling pathways and in humans, alterations in cilia function lead to several neural abnormalities. In this study we focused on Arl13b, a gene known to regulate ciliogenesis. Functional alterations in this gene?s activity have been associated with Joubert syndrome, a rare ciliopathy affecting brain morphology. Interestingly, we found that in Arl13 null mouse embryos theorientation of the optic vesicles is inverted, such that the lens is abnormally surrounded by an inverted optic vesicle whose retina pigmented epithelium is oddly facing the surface ectoderm. We show that this unusual phenotype is consequence of miss-regulation of Sonic hedgehog signaling. Loss of Arl13b leads to disruption of optic vesicles patterning and expansion of ventral fates. We also demostrate that the Arl13b-/- eye phenotype can be rescued by deletion of Gli2, a downstream effector of the Shh pathway.These in vivo studies are supported by in vitro results using CRISPR/Cas9 and cultured eye organoids derived from Arl13b-/-ESCs. Using these in vitro tools we demonstrate that chemical perturbation of the Shh signaling pathway is sufficient to disrupt normal optic cup morphogenesis. Together, these results suggest that Arl13b activity is required for proper morphogenesis and dorsal-ventral patterning of the optic vesicles.