Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex^1,2, yet all derive from neural progenitors of the embryonic dorsal telencephalon^3,4. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons. We generated over a dozen temporally inducible mouse Cre and Flp knock-in driver lines to enable the combinatorial targeting of major progenitor types and projection classes. Combinatorial strategies confer viral access to subsets of pyramidal neurons defined by developmental origin, marker expression, anatomical location and projection targets. These strategies establish an experimental framework for understanding the hierarchical organization and developmental trajectory of subpopulations of pyramidal neurons that assemble cortical processing networks and output channels.

不同类型的谷氨酸能锥体神经元介导大脑皮层的无数处理流和输出通道^1,2 ，但全部都源自胚胎背侧端脑^3,4的神经祖细胞。在这里，我们根据锥体神经元的发育和分子程序建立了遗传策略和工具，用于解剖和绘制锥体神经元亚群的命运图谱。我们利用关键转录因子和效应基因来系统地靶向祖细胞中的时间模式程序和有丝分裂后神经元中的分化程序。我们生成了十多个临时诱导型小鼠 Cre 和 Flp 敲入驱动程序系，以实现主要祖细胞类型和投射类别的组合靶向。组合策略使病毒能够进入由发育起源、标记表达、解剖位置和投射目标定义的锥体神经元子集。这些策略建立了一个实验框架，用于理解组装皮质处理网络和输出通道的锥体神经元亚群的层次组织和发育轨迹。