Retinoid-Related Orphan Receptor α Controls the Early Steps of Purkinje Cell Dendritic Differentiation

Abstract

Dendritic differentiation involves both regressive and growth events. The mechanisms controlling the regressive events are poorly understood. This study is aimed at determining the role of the nuclear receptor retinoid-related orphan receptor α (RORα) in Purkinje cell (PC) dendritic differentiation in organotypic cultures. As observed in vivo, in these cultures, fusiform PCs with embryonic bipolar shape undergo regression before the outgrowth of the ultimate dendritic tree. We show that lentiviral-mediated hRORα1 overexpression in fusiform PCs leads to a cell-autonomous accelerated progression of dendritic differentiation. In addition, RORα is necessary for the PC regressive events: whereas staggerer RORα-deficient PCs remain in the embryonic fusiform stage, replacement of hRORα1 restores normal dendritogenesis. These results demonstrate that RORα expression in fusiform PCs is crucial for the dendritic regression and progression of the following step of extension of dendritic processes. However, it does not seem to participate to the last stage of dendritic growth. This study identifies RORα as a nuclear receptor crucial for the control of dendritic remodeling during development.