ROR alpha Regulates Multiple Aspects of Dendrite Development in Cerebellar Purkinje Cells In Vivo

• Published in: The Journal of neuroscience 2015-09, Vol.35 (36), p.12518-12534
• Main Authors: Takeo, Yukari H, Kakegawa, Wataru, Miura, Eriko, Yuzaki, Michisuke
• Format: Article
• Language: English
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.007515.2015

The establishment of cell-type-specific dendritic arbors is fundamental for proper neural circuit formation. Here, using temporal- and cell-specific knock-down, knock-out, and overexpression approaches, we show that multiple aspects of the dendritic organization of cerebellar Purkinje cells (PCs) are controlled by a single transcriptional factor, retinoic acid-related orphan receptor-alpha (ROR alpha ), a gene defective in staggerer mutant mice. As reported earlier, ROR alpha was required for regression of primitive dendrites before postnatal day 4 (P4). ROR alpha was also necessary for PCs to form a single Purkinje layer from PO to P4. The knock-down of RORa from P4 impaired the elimination of perisomatic dendrites and maturation of single stem dendrites in PCs at P8. Filopodia and spines were also absent in these PCs. The knock-down of ROR alpha from P8 impaired the formation and maintenance of terminal dendritic branches of PCs at P14. Finally, even after dendrite formation was completed at P21, ROR alpha was required for PCs to maintain dendritic complexity and functional synapses, but their mature innervation pattern by single climbing fibers was unaffected. Interestingly, overexpression of ROR alpha in PCs at various developmental stages did not facilitate dendrite development, but had specific detrimental effects on PCs. Because ROR alpha deficiency during development is closely related to the severity of spinocerebellar ataxia type 1, delineating the specific roles of ROR alpha in PCs in vivo at different time windows during development and throughout adulthood would facilitate our understanding of the pathogenesis of cerebellar disorders.