Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Neurosciences Graduate Program, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037, USA.
Science. 2021 Apr 23;372(6540):385-393. doi: 10.1126/science.abe0690.
Motor and sensory functions of the spinal cord are mediated by populations of cardinal neurons arising from separate progenitor lineages. However, each cardinal class is composed of multiple neuronal types with distinct molecular, anatomical, and physiological features, and there is not a unifying logic that systematically accounts for this diversity. We reasoned that the expansion of new neuronal types occurred in a stepwise manner analogous to animal speciation, and we explored this by defining transcriptomic relationships using a top-down approach. We uncovered orderly genetic tiers that sequentially divide groups of neurons by their motor-sensory, local-long range, and excitatory-inhibitory features. The genetic signatures defining neuronal projections were tied to neuronal birth date and conserved across cardinal classes. Thus, the intersection of cardinal class with projection markers provides a unifying taxonomic solution for systematically identifying distinct functional subsets.
脊髓的运动和感觉功能是由源自不同祖细胞谱系的主要神经元群体介导的。然而,每个主要神经元类群都由具有不同分子、解剖和生理特征的多个神经元类型组成,而且没有一个统一的逻辑可以系统地解释这种多样性。我们推断,新神经元类型的扩展是分阶段进行的,类似于动物物种形成,我们通过使用自上而下的方法定义转录组关系来探索这一点。我们发现有序的遗传层次,按其运动-感觉、局部-长程和兴奋-抑制特征依次划分神经元群。定义神经元投射的遗传特征与神经元的出生日期有关,并在主要神经元类群中保守。因此,主要神经元类群与投射标记的交叉为系统地识别不同功能亚群提供了一个统一的分类解决方案。
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