Prospective separation and transcriptome analyses of cortical projection neurons and interneurons based on lineage tracing by Tbr2 (Eomes)‐GFP/Dcx‐mRFP reporters

In the cerebral cortex, projection neurons and interneurons work coordinately to establish neural networks for normal cortical functions. While the specific mechanisms that control productions of projection neurons and interneurons are beginning to be revealed, a global characterization of the molecular differences between these two neuron types is crucial for a more comprehensive understanding of their developmental specifications and functions. In this study, using lineage tracing power of combining Tbr2(Eomes)-GFP and Dcx-mRFP reporter mice, we prospectively separated intermediate progenitor cell (IPC)-derived neurons (IPNs) from non-IPC-derived neurons (non-IPNs) of the embryonic cerebral cortex. Molecular characterizations revealed that IPNs and non-IPNs were enriched with projection neurons and interneurons, respectively. Expression profiling documented cell-specific genes including differentially expressed transcriptional regulators that might be involved in cellular specifications, for instance, our data found that SOX1 and SOX2, which were known for important functions in neural stem/progenitor cells, continued to be expressed by interneurons but not by projection neurons. Transcriptome analyses of cortical neurons isolated at different stages of neurogenesis revealed distinct temporal patterns of expression of genes involved in early-born or late-born neuron specification. These data present a resource useful for further investigation of the molecular regulations and functions of projection neurons and interneurons. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 587–599, 2016