Identification of genes involved in GABAergic Wiring

How neurons are wired to form precise circuits is crucial to understand the development of cortical functions. Glutamatergic pyramidal cell and GABAergic interneuron wire up the cortex through differentiated cellular events. However, little is known about the molecular mechanisms that underlie the unique features of interneuron wiring. We performed a high-throughput genomic screen for genes upregulated specifically during GABAergic wiring. We used fluorescence-activated cell sorting (FACS) to isolate pyramidal cells and interneurons using mice in which these populations of cells are labeled with GFP (NexCre;RCE and Nkx2-1Cre;RCE, respectively) at two different postnatal stages (P0 and P12 for pyramidal cells and P0 and P10 for interneurons), and subsequently carried out transcriptome analyses

神经元如何搭建精确环路，对于解析大脑皮层功能的发育进程至关重要。谷氨酸能锥体神经元（glutamatergic pyramidal cell）与γ-氨基丁酸能中间神经元（GABAergic interneuron）通过差异化的细胞事件构建大脑皮层环路。然而，目前学界对中间神经元环路构建独特特征背后的分子机制仍知之甚少。我们针对γ-氨基丁酸能环路发育过程中特异性上调的基因开展了高通量基因组筛选：首先借助荧光激活细胞分选术（fluorescence-activated cell sorting, FACS），利用两种分别标记目标细胞群体的绿色荧光蛋白（GFP）小鼠品系——NexCre;RCE（标记锥体神经元）与Nkx2-1Cre;RCE（标记中间神经元）——在两个不同的产后阶段分离细胞：锥体神经元的取样时间点为出生后第0天（P0）与出生后第12天（P12），中间神经元的取样时间点为出生后第0天（P0）与出生后第10天（P10）；随后对分离得到的细胞进行转录组分析。