RORα Coordinates Thalamic and Cortical Maturation to Instruct Barrel Cortex Development

Abstract

The retinoic acid-related orphan receptor alpha (RORα) is well-known for its role in cerebellar development and maturation as revealed in staggerer mice. However, its potential involvement in the development of other brain regions has hardly been assessed. Here, we describe a new role of RORα in the development of primary somatosensory maps. Staggerer mice showed a complete disruption of barrels in the somatosensory cortex and of barreloids in the thalamus. This phenotype results from a severe reduction of thalamocortical axon (TCA) branching and a defective maturation of layer IV cortical neurons during postnatal development. Conditional deletion of RORα was conducted in the thalamus or the cortex to determine the specific contribution of RORα in each of these structures to these phenotypes. This showed that RORα is cell-autonomously required in the thalamus for the organization of TCAs into periphery-related clusters and in the somatosensory cortex for the dendritic maturation of layer IV neurons. Microarray analyses revealed that Sema7a, Neph, and Adcy8 are RORα regulated genes that could be implicated in TCA and cortical maturation. Overall, our study outlines a new role of RORα for the coordinated maturation of the somatosensory thalamus and cortex during the assembly of columnar barrel structures.

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