Leon Walter R Mancia, Steffen David M, Dale-Huang Fiona, Rakela Benjamin, Breevoort Arnar, Romero-Rodriguez Ricardo, Hasenstaub Andrea R, Stryker Michael P, Weiner Joshua A, Alvarez-Buylla Arturo
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.
Iowa Neuroscience Institute, The University of Iowa, Iowa City, IA 52242.
bioRxiv. 2023 Feb 6:2023.02.03.526887. doi: 10.1101/2023.02.03.526887.
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. Previously, we showed 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. Here we show that the sole deletion of the Pcdhγc4 isoform, but not of the other 21 isoforms in the Pcdhγ gene cluster, increased cIN cell death in mice during the normal period of programmed cell death. Viral expression of the isoform rescued transplanted cINs lacking from cell death. We conclude that specifically plays a critical role in regulating the survival of cINs during their normal period of cell death. This demonstrates a novel specificity in the role of isoforms in cortical development.
皮质功能严重依赖于抑制性/兴奋性平衡。皮质抑制性中间神经元（cINs）在前脑腹侧产生并迁移至皮质，在皮质中其数量通过程序性细胞死亡进行调节。此前，我们发现成簇的γ原钙黏蛋白（）缺失，而非α或β簇中的基因缺失，会显著增加小鼠中依赖cIN BAX的细胞死亡。在此我们表明，仅缺失Pcdhγc4亚型，而非Pcdhγ基因簇中的其他21种亚型，会在程序性细胞死亡的正常时期增加小鼠中的cIN细胞死亡。该亚型的病毒表达挽救了缺乏该亚型的移植cINs免于细胞死亡。我们得出结论，在cINs正常细胞死亡时期， 特异性地在调节其存活中起关键作用。这证明了 亚型在皮质发育中的作用具有新的特异性。
