Molecular Gradients and Compartments in the Embryonic Primate Cerebral Cortex

The mature cerebral cortex is divided into morphologically distinct, functionally dedicated and stereotypically connected cortical areas. How might such functional domains arise during development? To investigate possible intrinsic programs within the embryonic cerebral cortex we examined patterns of gene expression early in corticogenesis. We performed these studies using the developing macaque monkey because of the size, complexity, areal make-up and the extended nature of its cortical development. Here, we present results for two types of molecules. (i) Transcription factors -- gene products that bind DNA and activate transcription, directing cellular fates through cascades of gene expression. We find that the transcription factors TBr-1, Lhx-2, Emx-1 and a novel POU domain-containing gene are differentially expressed within the forming primate forebrain, and are present in gradients across the neocortex. (ii) The EphA receptor tyrosine kinases -- gene products that mediate cellular recognition in many embryonic systems. Individual members of this family are expressed during primate corticogenesis in pronounced gradients and/or well-defined compartments with distinct boundaries. Together, these results suggest that at least two modes of grouping cells within the neocortex exist: the graded patterning of cells across its full anteroposterior extent and the parcellation of cells into defined domains. Moreover, emergence of molecular differences between regions of the cortical plate, prior to the arrival of afferent and formation of efferent connections, suggests that the initial cellular parcellation in the telencephalon is cell-autonomously regulated. This initial independence from peripheral influences supports the existence of an intrinsic protomap that may function both to differentially attract and respond to specific afferents, thus predicting the functional map of the mature cortex.