The generation of layer-specific cortical neurons is fundamental to the circuitry of the developing and adult brain. Although the intrinsic drivers of neuronal specification are becoming increasingly understood, the extrinsic signals that guide migration and consolidate post-mitotic neuronal identity are less clear. In this issue (), Shanthini Sockanathan and colleagues investigate the role of endogenous retinoic acid (RA) signalling in regulating the radial migration and laminar fate of post-mitotic cortical neurons. Using a dominant-negative RA receptor construct, the authors show that ablation of RA signalling in mouse embryos in utero not only delays migration of subsets of cortical neurons, but also results in a failure to maintain their correct regional identity following migration. This phenotype can be partially rescued by stabilised β-catenin, which the authors show is normally maintained by RA signalling. This work sheds light on the extrinsic mechanisms that control cortical neuronal development and has important implications for disorders in which cortical neuronal circuitry is de-regulated.
