Prospective separation and transcriptome analyses of cortical projection neurons and interneurons based on lineage tracing by Tbr2 (Eomes)-GFP/Dcx-mRFP reporters.
Prospective separation and transcriptome analyses of cortical projection neurons and interneurons based on lineage tracing by Tbr2 (Eomes)-GFP/Dcx-mRFP reporters.
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DOI：
10.1002/dneu.22332
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发表时间：
2016-06
影响因子：
3
通讯作者：
Lu Q
中科院分区：
文献类型：
--
作者：
Liu J;Wu X;Zhang H;Qiu R;Yoshikawa K;Lu Q
在大脑皮层，投射神经元和中间神经元协同工作，为正常的皮质功能建立神经网络。虽然控制投射神经元和中间神经元产生的具体机制开始被揭示，但这两种神经元之间的分子差异的全球特征对于更全面地了解它们的发育规格和功能是至关重要的。在这项研究中，利用结合Tbr2(EBES)-GFP和DCX-MRFP报告小鼠的谱系追踪能力，我们前瞻性地分离了胚胎大脑皮层的中间前体细胞(IPC)来源的神经元(IPN)和非IPC来源的神经元(Non-IPN)。分子表征表明，IPN和非IPN分别富含投射神经元和中间神经元。例如，我们的数据发现，已知在神经干细胞/祖细胞中具有重要功能的SOX1和SOX2继续由中间神经元表达，而不是由投射神经元表达。对神经发生不同阶段分离的皮质神经元的转录组分析显示，与早出生或晚出生神经元规格有关的基因的表达具有不同的时间模式。这些数据为进一步研究投射神经元和中间神经元的分子调控和功能提供了有用的资源。
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.