The human brain is subdivided into distinct anatomical structures, including the neocortex, which in turn encompasses dozens of distinct specialized cortical areas. Early morphogenetic gradients are known to establish early brain regions and cortical areas, but how early patterns result in finer and more discrete spatial differences remains poorly understood¹. Here we use single-cell RNA sequencing to profile ten major brain structures and six neocortical areas during peak neurogenesis and early gliogenesis. Within the neocortex, we find that early in the second trimester, a large number of genes are differentially expressed across distinct cortical areas in all cell types, including radial glia, the neural progenitors of the cortex. However, the abundance of areal transcriptomic signatures increases as radial glia differentiate into intermediate progenitor cells and ultimately give rise to excitatory neurons. Using an automated, multiplexed single-molecule fluorescent in situ hybridization approach, we find that laminar gene-expression patterns are highly dynamic across cortical regions. Together, our data suggest that early cortical areal patterning is defined by strong, mutually exclusive frontal and occipital gene-expression signatures, with resulting gradients giving rise to the specification of areas between these two poles throughout successive developmental timepoints.

人脑被细分为不同的解剖结构，包括新皮质，而新皮质又包含数十个不同的专门皮质区域。已知早期形态发生梯度可以建立早期大脑区域和皮层区域，但早期模式如何导致更精细和更离散的空间差异仍然知之甚少¹. 在这里，我们使用单细胞 RNA 测序来分析高峰神经发生和早期胶质发生期间的十个主要大脑结构和六个新皮质区域。在新皮质内，我们发现在妊娠中期早期，大量基因在所有细胞类型的不同皮质区域中差异表达，包括放射状神经胶质，皮质的神经祖细胞。然而，随着放射状胶质细胞分化为中间祖细胞并最终产生兴奋性神经元，区域转录组特征的丰度增加。使用自动化、多路复用的单分子荧光原位杂交方法，我们发现层状基因表达模式在皮层区域是高度动态的。总之，我们的数据表明，早期的皮层区域模式是由强定义的，