Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers are adjusted by programmed cell death. Here, we show that loss of clustered gamma protocadherins (Pcdhg), but not of genes in the alpha or beta clusters, increased dramatically cIN BAX-dependent cell death in mice. Surprisingly, electrophysiological and morphological properties of Pcdhg-deficient and wild-type cINs during the period of cIN cell death were indistinguishable. Co-transplantation of wild-type with Pcdhg-deficient interneuron precursors further reduced mutant cIN survival, but the proportion of mutant and wild-type cells undergoing cell death was not affected by their density. Transplantation also allowed us to test for the contribution of Pcdhg isoforms to the regulation of cIN cell death. We conclude that Pcdhg, specifically Pcdhgc3, Pcdhgc4, and Pcdhgc5, play a critical role in regulating cIN survival during the endogenous period of programmed cIN death.

中文翻译：

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簇状γ-原钙粘蛋白调节皮质中间神经元程序性细胞死亡

皮质功能关键取决于抑制/兴奋平衡。皮质抑制性中间神经元（cIN）诞生于腹侧前脑，并迁移到皮质，其数量通过程序性细胞死亡进行调整。在这里，我们发现，簇状γ原钙粘蛋白（Pcdhg）的丢失，而不是α或β簇中基因的丢失，显着增加了小鼠中cIN BAX依赖性细胞死亡。令人惊讶的是，Pcdhg 缺陷型和野生型 cIN 在 cIN 细胞死亡期间的电生理学和形态学特性无法区分。野生型与缺乏 Pcdhg 的中间神经元前体的共移植进一步降低了突变型 cIN 的存活率，但发生细胞死亡的突变型和野生型细胞的比例不受其密度的影响。移植还使我们能够测试 Pcdhg 亚型对 cIN 细胞死亡调节的贡献。我们得出的结论是，Pcdhg，特别是 Pcdhgc3、Pcdhgc4 和 Pcdhgc5，在内源性程序性 cIN 死亡期间，在调节 cIN 存活方面发挥着关键作用。