Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States.
Department of Physiology and Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, United States.
Elife. 2020 Jul 7;9:e55374. doi: 10.7554/eLife.55374.
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 (), 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 -deficient and wild-type cINs during the period of cIN cell death were indistinguishable. Co-transplantation of wild-type with -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 isoforms to the regulation of cIN cell death. We conclude that , specifically , , and , play a critical role in regulating cIN survival during the endogenous period of programmed cIN death.
皮质功能严重依赖于抑制/兴奋平衡。皮质抑制性中间神经元（cIN）在腹侧前脑中产生并迁移到皮质，其数量通过程序性细胞死亡进行调整。在这里，我们表明，聚集的γ原钙黏蛋白（）缺失，但α或β簇中的基因缺失不会导致小鼠 cIN 中 BAX 依赖性细胞死亡显著增加。令人惊讶的是，-缺陷型和野生型 cIN 在 cIN 细胞死亡期间的电生理和形态特性没有区别。野生型与 -缺陷型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，但突变型和野生型细胞经历细胞死亡的比例不受其密度的影响。移植还使我们能够测试同种型对 cIN 细胞死亡调节的贡献。我们得出结论，特别是 、 、和 ，在调节内源性程序性 cIN 死亡期间的 cIN 存活中发挥关键作用。
