Molecular Markers Distinguishing Supragranular and Infragranular Layers in the Human Prefrontal Cortex

The human neocortex is organized into six layers that are differentiated by the size and packing density of their constituent neurons. The gene products that guide the establishment of this lamination have been studied extensively, but the gene expression gradients present across the layers of the adult human neocortex are mostly unknown. As the supragranular (SG) and infragranular (IG) layers of the human prefrontal cortex (PFC) differ in their connectivity and developmental time course, we hypothesized that the SG and IG layers will show distinct differences in their transcriptomes. To test this prediction, we used laser capture microdissection coupled with DNA microarray transcriptome profiling. Sixty-nine genes exhibited robust and highly consistent expression differences between the SG and IG layers. For six selected markers, in addition to validating the microarray findings, in situ hybridization revealed a complex, subpopulation-specific neuronal distribution. The markers we identified are likely to be related to the functional differences between the SG and IG layers of the human PFC and can be used for assessing alterations in structure and function of this cortical region in human brain disorders.