During brain development, the sequence of developmental steps and the underlying transcriptional regulatory logic are largely conserved across species. However, the temporal unfolding of developmental programs varies dramatically across species and within a given species varies across brain regions and cell identities. The maturation of neurons in the human cerebral cortex is particularly slow and lasts for many years compared with only a few weeks for the corresponding mouse neurons. The mechanisms setting the ‘schedule’ of neuronal maturation remain unclear but appear to be linked to a cell-intrinsic ‘clock’. Here, we discuss recent findings that highlight a role for epigenetic factors in the timing of neuronal maturation. Manipulations of those factors in stem cell-based models can override the intrinsic pace of neuronal maturation, including its protracted nature in human cortical neurons. We then contextualize the epigenetic regulation of maturation programs with findings from other model systems and propose potential interactions between epigenetic pathways and other drivers of developmental rates.

中文翻译：

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表观遗传控制和神经元成熟时间的操纵

在大脑发育过程中，发育步骤的顺序和潜在的转录调节逻辑在不同物种之间很大程度上是保守的。然而，发育程序的时间展开在不同物种之间存在显着差异，并且在特定物种内，不同大脑区域和细胞身份也存在差异。人类大脑皮层神经元的成熟特别缓慢，并且持续多年，而相应的小鼠神经元只有几周的成熟。设定神经元成熟“时间表”的机制仍不清楚，但似乎与细胞固有的“时钟”有关。在这里，我们讨论最近的发现，这些发现强调了表观遗传因素在神经元成熟时间中的作用。在基于干细胞的模型中操纵这些因素可以超越神经元成熟的内在速度，包括其在人类皮质神经元中的长期性质。然后，我们将成熟程序的表观遗传调控与其他模型系统的发现联系起来，并提出表观遗传途径与发育速率的其他驱动因素之间的潜在相互作用。