Subplate

Abstract: The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Abstract: The cytological organization and the timetable of emergence and dissolution of the transient subplate zone subjacent to the developing visual and somatosensory cortex were studied in a series of human and monkey fetal brains. Cerebral walls processed with Nissl, Golgi, electron-microscopic, and histochemical methods show that this zone consists of migratory and postmigratory neurons, growth cones, loosely arranged axons, dendrites, synapses, and glial cells. In both species the subplate zone becomes visible at the beginning of the mid-third of gestation as a cell-poor/fiber-rich layer situated between the intermediate zone and the developing cortical plate. The subplate zone appears earlier in the somatosensory than in the visual area and reaches maximal width at the beginning of the last third of gestation in both regions. At the peak of its size the ratio between the width of the subplate zone and cortical plate in the somatosensory cortex is 2:1 in monkey and 4:1 in man while in the occipital lobe these structures have about equal width in both species. The dissolution of the subplate zone begins during the last third of gestation with degeneration of some subplate neurons and the relocation of fiber terminals into the cortex. The subplate zone disappears faster in the visual than in the somatosensory area. The present results together with our previous findings support the hypothesis that the subplate zone may serve as a “waiting” compartment for transient cellular interactions and a substrate for competition, segregation, and growth of afferents originated sequentially from the brain stem, basal forebrain, thalamus, and from the ipsi- and contralateral cerebral hemisphere. After a variable and partially overlapping time period, these fibers enter the cortical plate while the subplate zone disappears leaving only a vestige of cells scattered throughout the subcortical white matter. A comparison between species indicates that the size and duration of the subplate zone increases during mammalian evolution and culminates in human fetuses concomitantly with an enlargement of cortico-cortical fiber systems. The regional difference in the size, pattern, and resolution of the subplate zone correlates also with the pattern of cerebral convolutions. Our findings indicate that, contrary to prevailing notions, the subplate may not be a vestige of the phylogenetically old network but a transient embryonic structure that expanded during evolution to subserve the increasing number of its connections.

Abstract: Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaudal-ventrorostral axis and undergoes region-specific rolling morphogenesis that generates a semispherical structure. The neuroepithelium self-forms a multilayered structure including three neuronal zones (subplate, cortical plate, and Cajal-Retzius cell zones) and three progenitor zones (ventricular, subventricular, and intermediate zones) in the same apical-basal order as seen in the human fetal cortex in the early second trimester. In the cortical plate, late-born neurons tend to localize more basally to early-born neurons, consistent with the inside-out pattern seen in vivo. Furthermore, the outer subventricular zone contains basal progenitors that share characteristics with outer radial glia abundantly found in the human, but not mouse, fetal brain. Thus, human neocorticogenesis involves intrinsic programs that enable the emergence of complex neocortical features.