Optic vesicle morphogenesis requires primary cilia.

Abstract Arl13b is a gene known to regulate ciliogenesis. Functional alterations in this gene’s activity have been associated with Joubert syndrome. We found that in Arl13 null mouse embryos the orientation of the optic cup is inverted, such that the lens is abnormally surrounded by an inverted optic vesicle whose retina pigmented epithelium is oddly facing the surface ectoderm. Loss of Arl13b leads to disruption of optic vesicles patterning and expansion of ventral fates. We show that this phenotype is consequence of miss-regulation of Sonic hedgehog signaling and demonstrate that the Arl13b-/- eye phenotype can be rescued by deletion of Gli2, a downstream effector of the Shh pathway. This work identified an unexpected role of primary cilia during the morphogenetic movements required for the formation of the eye.