Cortical patterning is likely a result of intrinsic signaling, controlled in part by graded expression of transcription factors during early cortical development, followed by extrinsic signaling from thalamic afferents after the start of corticogenesis46–49. We sought to identify putative patterning centers, defined as regions where many genes show peak expression tapering off with distance, for each layer of the human prenatal cortex using an unbiased approach. To do so, we first assigned 3D coordinates to each cortical sample, and then identified the location of maximum expression of the most graded genes in all four brains. In several layers, including CPo and SZi (Fig. 5a–b), the majority of these genes peaked in the frontal or temporal lobes. Rather than peaks in presumptive functional areas, this suggests a generally rostro-caudal organization axis that is better characterized as fronto-temporal, following the contour of the developing cortex. To identify such fronto-temporal patterning genes directly, we correlated gene expression in each cortical layer against the angular position of each neocortical region, as illustrated schematically in Figure 5c. All layers contained gradient genes conserved across all
