Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. Cortical neurons are born during embryonic development, and their maturation extends into postnatal life. The regulatory strategies underlying progressive neuronal development and maturation remain unclear. Here we present an integrated single-cell epigenomic and transcriptional analysis of individual mouse and marmoset cortical neuron classes, spanning both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We found that, in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use more widely shared and evolutionarily conserved molecular regulatory programs. In contrast, programs active during later neuronal maturation are more brain- and neuron-specific and more evolutionarily divergent. Our work uncovers a temporal shift in regulatory choices during neuronal diversification and maturation in both mice and marmosets, which likely reflects unique evolutionary constraints on distinct events of neuronal development in the neocortex.

哺乳动物新皮层神经元跨越任何组织中最多样化的细胞类型谱之一。皮质神经元在胚胎发育过程中诞生，它们的成熟延伸到出生后的生活。进行性神经元发育和成熟的基础调控策略仍不清楚。在这里，我们提出了对单个小鼠和狨猴皮层神经元类别的综合单细胞表观基因组和转录分析，涵盖身份获取的早期有丝分裂后阶段和神经元可塑性和电路整合的后期阶段。我们发现，在这两个物种中，控制泛神经元发育早期和晚期阶段的调控策略存在差异。早期有丝分裂后神经元使用更广泛共享和进化上保守的分子调节程序。相比之下，在后期神经元成熟过程中活跃的程序更具大脑和神经元特异性，并且在进化上更具差异性。我们的工作揭示了小鼠和狨猴神经元多样化和成熟过程中监管选择的​​时间变化，这可能反映了新皮质神经元发育的不同事件的独特进化限制。