Postmitotic control of sensory area specification during neocortical development

Abstract

The mammalian neocortex is subdivided into cytoarchitectural areas with distinct connectivity, gene expression and neural functions. Areal identity is initially specified by rostrocaudal and mediolateral gene expression gradients in neuroepithelial and radial glial progenitors (the 'protomap'). On further differentiation, distinct sets of gene expression gradients arise in intermediate progenitors and postmitotic neurons, and are necessary to implement areal specification. However, it is still unknown whether postmitotic gene expression gradients can determine areal identity independently of protomap gradients. Here we show, by cell type-restricted genetic loss- and gain-of-function, that high levels of postmitotic COUP-TFI (Nr2f1) expression are necessary and sufficient for the development of sensory (caudal) areal identity. Our data indicate a crucial role for postmitotic patterning genes in areal specification and reveal an unexpected plasticity in this process, which may account for complex and evolutionarily novel structures characteristic of the mammalian neocortex.