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Chunk #15 — Developmental gradients in neocortex

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Transcriptional landscape of the prenatal human brain.
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Some features of areal patterning appear to be preserved between mouse and human. For example, FGFR3, which is known to cause defects in human temporal cortex when mutated50, shows significant caudal enrichment in all germinal layers in both species (Fig. 5d–e). Conversely, CBLN2 shows rostral enrichment in human CPo (Fig. 5f) and in mouse (Fig. 5g), with an abrupt expression cutoff, implicating CBLN2 in early rostral patterning. Comparing these data to a microarray analysis of rostral versus caudal cortex in E14 mouse51 identified 20 additional genes with consistent rostrocaudal gradation between species (Suppl. Table 9; Suppl. Methods). Interestingly, we find more rostrally- than caudally-enriched genes in nearly every cortical layer (Fig. 5h), whereas two studies of gradient expression in prenatal mouse brain identified more49 or comparable51 caudally-enriched genes, indicating potential species differences related to areal patterning. This human frontal asymmetry is most apparent in the outer postmitotic layers MZ and CPo (Fig. 5i), and in SZo, which generates most superficial CP neurons in primate7,8, suggesting that these genes may play a part in the expansion and reorganization of human PFC8.