More than twelve morphologically and physiologically distinct subtypes of primary somatosensory neuron report salient features of our internal and external environments^1,2,3,4. It is unclear how specialized gene expression programs emerge during development to endow these subtypes with their unique properties. To assess the developmental progression of transcriptional maturation of each subtype of principal somatosensory neuron, we generated a transcriptomic atlas of cells traversing the primary somatosensory neuron lineage in mice. Here we show that somatosensory neurogenesis gives rise to neurons in a transcriptionally unspecialized state, characterized by co-expression of transcription factors that become restricted to select subtypes as development proceeds. Single-cell transcriptomic analyses of sensory neurons from mutant mice lacking transcription factors suggest that these broad-to-restricted transcription factors coordinate subtype-specific gene expression programs in subtypes in which their expression is maintained. We also show that neuronal targets are involved in this process; disruption of the prototypic target-derived neurotrophic factor NGF leads to aberrant subtype-restricted patterns of transcription factor expression. Our findings support a model in which cues that emanate from intermediate and final target fields promote neuronal diversification in part by transitioning cells from a transcriptionally unspecialized state to transcriptionally distinct subtypes by modulating the selection of subtype-restricted transcription factors.

超过 12 种形态和生理上不同的初级体感神经元亚型报告了我们内部和外部环境的显着特征^1,2,3,4. 尚不清楚在发育过程中如何出现专门的基因表达程序以赋予这些亚型独特的特性。为了评估主要体感神经元的每个亚型转录成熟的发育进程，我们生成了穿越小鼠初级体感神经元谱系的细胞的转录组图谱。在这里，我们表明，体感神经发生导致神经元处于转录非特化状态，其特征是转录因子的共表达，随着发育的进行，这些转录因子变得仅限于选择亚型。对缺乏转录因子的突变小鼠的感觉神经元进行单细胞转录组分析表明，这些从广泛到受限的转录因子在维持其表达的亚型中协调亚型特异性基因表达程序。我们还表明神经元靶标参与了这个过程。原型靶源性神经营养因子 NGF 的破坏导致转录因子表达的异常亚型限制模式。我们的研究结果支持一个模型，其中来自中间和最终靶场的线索通过调节亚型限制转录因子的选择，部分通过将细胞从转录非特化状态转变为转录不同亚型来促进神经元多样化。我们还表明神经元靶标参与了这个过程。原型靶源性神经营养因子 NGF 的破坏导致转录因子表达的异常亚型限制模式。我们的研究结果支持一个模型，其中来自中间和最终靶场的线索通过调节亚型限制转录因子的选择，部分通过将细胞从转录非特化状态转变为转录不同亚型来促进神经元多样化。我们还表明神经元靶标参与了这个过程。原型靶源性神经营养因子 NGF 的破坏导致转录因子表达的异常亚型限制模式。我们的研究结果支持一个模型，其中来自中间和最终靶场的线索通过调节亚型限制转录因子的选择，部分通过将细胞从转录非特化状态转变为转录不同亚型来促进神经元多样化。