Diverse γ-aminobutyric acid (GABA)-ergic interneurons provide different modes of inhibition to support circuit operation in the neocortex. However, the cellular and molecular mechanisms underlying the systematic generation of assorted neocortical interneurons remain largely unclear. Here we show that NKX2.1-expressing radial glial progenitors (RGPs) in the mouse embryonic ventral telencephalon divide progressively to generate distinct groups of interneurons, which occupy the neocortex in a time-dependent, early inside-out and late outside-in, manner. Notably, the late-born chandelier cells, one of the morphologically and physiologically highly distinguishable GABAergic interneurons, arise reliably from continuously dividing RGPs that produce non-chandelier cells initially. Selective removal of Partition defective 3, an evolutionarily conserved cell polarity protein, impairs RGP asymmetric cell division, resulting in premature depletion of RGPs towards the late embryonic stages and a consequent loss of chandelier cells. These results suggest that consecutive asymmetric divisions of multipotent RGPs generate diverse neocortical interneurons in a progressive manner.

中文翻译：

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多能神经祖细胞的渐进分裂在新皮层中产生迟来的枝形吊灯细胞。

多种γ-氨基丁酸（GABA）增能中神经元提供不同的抑制模式，以支持新皮层中的电路操作。然而，各种各样的新皮层中间神经元系统生成的细胞和分子机制仍不清楚。在这里，我们显示了在小鼠胚胎腹侧端脑中表达NKX2.1的放射状神经胶质祖细胞（RGPs）逐渐分裂，以生成不同的中间神经元群，这些中间神经元在时间依赖性，早期内外和晚期外内中占据了新皮层，方式。值得注意的是，在形态和生理上高度可区分的GABA能中间神经元之一的后期枝形吊灯细胞，是通过连续分裂最初产生非枝形吊灯细胞的RGP可靠地产生的。选择性清除分区缺陷3，进化上保守的细胞极性蛋白会损害RGP的不对称细胞分裂，从而导致RGPs在早期胚胎阶段过早耗尽，从而导致枝形吊灯细胞丢失。这些结果表明，多能RGP的连续不对称分裂以渐进方式产生了多种新皮层间神经元。