The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
Development. 2019 Mar 27;146(12):dev173807. doi: 10.1242/dev.173807.
The coordinated spatial and temporal regulation of gene expression in the vertebrate neural tube determines the identity of neural progenitors and the function and physiology of the neurons they generate. Progress has been made deciphering the gene regulatory programmes that are responsible for this process; however, the complexity of the tissue has hampered the systematic analysis of the network and the underlying mechanisms. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions of the developing mouse neural tube between embryonic days 9.5-13.5. We confirmed that the data accurately recapitulates neural tube development, allowing us to identify new markers for specific progenitor and neuronal populations. In addition, the analysis highlighted a previously underappreciated temporal component to the mechanisms that generate neuronal diversity, and revealed common features in the sequence of transcriptional events that lead to the differentiation of specific neuronal subtypes. Together, the data offer insight into the mechanisms that are responsible for neuronal specification and provide a compendium of gene expression for classifying spinal cord cell types that will support future studies of neural tube development, function and disease.
脊椎动物神经管中基因表达的时空协调调节决定了神经祖细胞的身份，以及它们所产生的神经元的功能和生理学。在解析负责这一过程的基因调控程序方面已经取得了进展；然而，组织的复杂性阻碍了对网络和基础机制的系统分析。为了解决这个问题，我们使用单细胞 mRNA 测序技术对胚胎第 9.5-13.5 天之间发育中的小鼠神经管的颈椎和胸椎区域进行了分析。我们证实，这些数据准确地再现了神经管的发育过程，使我们能够识别特定祖细胞和神经元群体的新标记物。此外，该分析突出了产生神经元多样性的机制中以前未被充分认识的时间成分，并揭示了导致特定神经元亚型分化的转录事件序列中的共同特征。总之，这些数据为负责神经元特化的机制提供了深入的了解，并为脊髓细胞类型的分类提供了基因表达的纲要，这将支持未来对神经管发育、功能和疾病的研究。
