Activated retinoid receptors are required for the migration and fate maintenance of subsets of cortical neurons.

Abstract

Layer-specific cortical neurons are essential components of local, intracortical and subcortical circuits and are specified by complex signaling pathways acting on cortical progenitors. However, whether extrinsic signals contribute to postmitotic cortical neuronal development is unclear. Here we show in mice that retinoic acid (RA) receptors are activated in newly born migrating cortical neurons indicative of endogenous RA in the cortex. Disruption of RA signaling in postmitotic neurons by dominant-negative retinoid receptor RAR403 expression specifically delays late-born cortical neuron migration in vivo. Moreover, prospective layer V-III neurons that express RAR403 fail to maintain their fates and instead acquire characteristics of layer II neurons. This latter phenotype is rescued by active forms of β-catenin at central and caudal but not rostral cortical regions. Taken together, these observations suggest that RA signaling pathways operate postmitotically to regulate the onset of radial migration and to consolidate regional differences in cortical neuronal identity.