A comparative molecular study of the amniote dorsal telencephalon

Evolutionary relationships among the structures of the dorsal telencephalon in mammals, birds, and reptiles are currently the subject of intense debate. One theory known as the Karten hypothesis proposes that the mammalian neocortex contains neurons that are homologous at the cell-type level to neurons within the avian telencephalon. The Karten hypothesis provides a set of specific proposals for cell type homology. The 'input' cell type---neurons receiving unimodal inputs from the sensory nuclei of the dorsal thalamus---is located in neocortical layer 4 in mammals, in the entopallium, field L, and intercalated nucleus of the hyperpallium (IHA) in birds. The 'output' cell type---neurons projecting to subcortical targets including the striatum, thalamus, and brainstem---is located in layer 5-6 of the mammalian neocortex, in the arcopallium and hyperpallium apicale (HA) in birds. These predictions in their specificity lend themselves very well to testing. We identified molecular markers of these cell types---'input' cells and 'output' cells---in the mammalian neocortex and isolated cDNA's for orthologous chicken genes. We then examined the expression pattern of each of these molecular markers within the chicken and turtle dorsal telencephalon. We found that two markers of the cells of neocortical layer 4---EAG2 and RORB---are expressed in the entopallium, field L, and IHA in the chicken. We also found that 12 markers of neurons in the deep neocortical layers---ER81, PCP4, FEZF2, TSHZ2, NECAB1, NEXIN, TOX, KIAA1913, SULF2, SYT6, and S100A10---are expressed in the arcopallium and HA in the chicken. Hence, the predictions of the Karten hypothesis are fully supported by these data. We also checked for the presence of a subset of these markers---EAG2, RORB, and ER81---in another bird, the zebrafinch, and in a reptile, the turtle. We found that in each group examined---mammals, birds, and reptiles---these cell types as defined by their expression of these molecular markers are conserved, but that they are organized in radically different ways. In the mouse, these cell types are segregated into separate layers of the neocortex; in the chicken and zebrafinch, these cell types are segregated into separate nuclei; and in the turtle, these cell types are segregated along the anterior-posterior axis in both the general cortex and the DVR.