Classically, three broad classes of projection neurons have been described for cortical excitatory neurons (Harris and Shepherd, 2015). Corticothalamic neurons project to the thalamus, their cell bodies occupy layer VI, and they express the transcription factor TBR1. Pyramidal tract neurons project to the spinal cord but often possess collateral projections to the thalamus and the medulla (Economo et al., 2018). These cells mainly occupy layer V and express transcription factors FEZF2 and BCL11B (previously known as Ctip2). Intratelencephalic (IT) neurons project to targets within the forebrain, including the striatum, ipsilateral, or contralateral hemisphere of the cortex. IT neurons are located in layers II–VI and are characterized by the expression of SATB2. Excellent reviews have provided detailed descriptions of the molecular markers of neurons in different layers and projection classes (Harris and Shepherd, 2015; Lodato and Arlotta, 2015; Molyneaux et al., 2007).
In the adult human, layer-specific dissections of the cortex followed by single-nucleus sequencing have identified human-specific markers of cortical layers in the medial temporal gyrus (Hodge et al., 2018), as well as new and previously described markers of layer identity (Zeng et al., 2012). Interestingly, most molecularly defined cell types in the adult human cortex appear to be present in more than one layer, suggesting that a combination of molecular identity and layer position may interact to generate a wide range of cell types both within and across cortical areas.
