Liver X receptor agonist treatment promotes the migration of granule neurons during cerebellar development

P>Liver X receptor alpha (LXR alpha) and beta (LXR beta) are members of the nuclear receptor superfamily of ligand-activated transcription factors, and expressed in the CNS. We have previously demonstrated that LXR beta is essential for migration of later-born neurons during cerebral cortex development, although the underlying mechanism is not clear. The cerebellum is organized in an exquisitely foliated structure with a simple layered cytoarchitecture and considered to be a good model to study morphogenesis of lamination and neuronal migration. Here, we found that T0901317, a potent LXR receptor agonist, administration to neonatal C57/BL6 mice, increased dendritic growth of Purkinje cell, although the appearance of the cerebellar cortex was not affected. We further demonstrated T0901317 treatment promoted the migration of granule neurons from the external granular layer to the internal granular layer during cerebellum development. Bergmann glial fibers serve as scaffolds for granule cells inward migration during cerebellum postnatal development. T0901317 treatment also inhibited premature differentiation of Bergmann glia during cerebellum development, which is related to the decreased levels of TGF-beta 1 and Smad4 in the cerebellum. Taken together, our findings suggest that endogenous LXR affects differentiation process of Bergmann glia and subsequently leads to promote the migration of granule neurons.