Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany.
Dev Neurobiol. 2022 May;82(4):345-363. doi: 10.1002/dneu.22876. Epub 2022 Apr 21.
The neocortex is considered the seat of higher cognitive function in humans. It develops from a sheet of neural progenitor cells, most of which eventually give rise to neurons. This process of cell fate determination is controlled by precise temporal and spatial gene expression patterns that in turn are affected by epigenetic mechanisms including Polycomb group (PcG) regulation. PcG proteins assemble in multiprotein complexes and catalyze repressive posttranslational histone modifications. Their association with neurodevelopmental disease and various types of cancer of the central nervous system, as well as observations in mouse models, has implicated these epigenetic modifiers in controlling various stages of cortex development. The precise mechanisms conveying PcG-associated transcriptional repression remain incompletely understood and are an active field of research. PcG activity appears to be highly context-specific, raising the question of species-specific differences in the regulation of neural stem and progenitor regulation. In this review, we will discuss our growing understanding of how PcG regulation affects human cortex development, based on studies in murine model systems, but focusing mostly on findings obtained from examining impaired PcG activity in the context of human neurodevelopmental disorders and cancer. Furthermore, we will highlight relevant experimental approaches for functional investigations of PcG regulation in human cortex development.
新皮层被认为是人类高级认知功能的所在地。它由一层神经祖细胞发育而来，其中大多数最终会产生神经元。这个细胞命运决定的过程受精确的时空基因表达模式的控制，而这些模式又受到表观遗传机制的影响，包括多梳组（PcG）调节。PcG 蛋白组装成多蛋白复合物，并催化抑制性的翻译后组蛋白修饰。它们与神经发育疾病和中枢神经系统的各种类型的癌症有关，以及在小鼠模型中的观察结果，表明这些表观遗传修饰物在控制皮质发育的各个阶段中起作用。传递 PcG 相关转录抑制的精确机制仍不完全清楚，是一个活跃的研究领域。PcG 活性似乎高度依赖于上下文，这就提出了一个问题，即在神经干细胞和祖细胞调控中是否存在物种特异性差异。在这篇综述中，我们将根据在小鼠模型系统中的研究，讨论我们对 PcG 调节如何影响人类大脑皮层发育的理解，重点是从研究人类神经发育障碍和癌症中观察到的 PcG 活性受损中获得的发现。此外，我们将突出介绍用于研究人类大脑皮层发育中 PcG 调节的功能的相关实验方法。
