Inhibitory interneurons are critical for maintaining the excitatory/inhibitory balance. During the development cortical interneurons originate from the ganglionic eminence and arrive at the dorsal cortex through two tangential migration routes. However, the mechanisms underlying the development of cortical interneurons remain unclear. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been shown to be involved in a variety of biological processes, including cell proliferation and migration, and plays an important role in the neurogenesis of cortical excitatory neurons. However, the function of PDK1 in interneurons is still unclear. Here, we reported that the disruption of Pdk1 in the subpallium achieved by crossing the Dlx5/6-Cre-IRES-EGFP line with Pdk1fl/fl mice led to the severely increased apoptosis of immature interneurons, subsequently resulting in a remarkable reduction in cortical interneurons. However, the tangential migration, progenitor pools and cell proliferation were not affected by the disruption of Pdk1. We further found the activity of AKT-GSK3β signaling pathway was decreased after Pdk1 deletion, suggesting it might be involved in the regulation of the survival of cortical interneurons. These results provide new insights into the function of PDK1 in the development of the telencephalon.

中文翻译：

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PDK1调节发育中的皮质神经元的存活。

抑制性中间神经元对于维持兴奋性/抑制性平衡至关重要。在发育过程中，皮质神经元起源于神经节突起，并通过两条切线迁移路径到达背皮质。但是，皮质神经元发育的机制尚不清楚。3-磷酸​​肌醇依赖性蛋白激酶-1（PDK1）已被证明参与多种生物学过程，包括细胞增殖和迁移，并在皮层兴奋性神经元的神经发生中起重要作用。但是，PDK1在中间神经元中的功能仍不清楚。在这里，我们报道了通过将Dlx5 / 6-Cre-IRES-EGFP系与Pdk1fl / fl小鼠杂交而破坏了骨膜下Pdk1，导致未成熟中神经元的细胞凋亡严重增加，随后导致皮质中间神经元的显着减少。但是，切向迁移，祖细胞库和细胞增殖不受Pdk1破坏的影响。我们还发现，Pdk1缺失后，AKT-GSK3β信号通路的活性降低，提示其可能参与了皮质神经元的存活调控。这些结果为PDK1在端脑发育中的功能提供了新的见解。