Setting the clock of neural progenitor cells during mammalian corticogenesis

Radial glial cells (RGCs) as primary neural stem cells in the developing mammalian cortex give rise to diverse types of neurons and glial cells according to sophisticated developmental programs with remarkable spatio-temporal precision. Recent studies suggest that regulation of the temporal competence of RGCs is a key mech-anism for the highly conserved and predictable development of the cerebral cortex. Various types of epigenetic regulations, such as DNA methylation, histone modifications, and 3D chromatin architecture, play a key role in shaping the gene expression pattern of RGCs. In addition, epitranscriptomic modifications regulate temporal pre -patterning of RGCs by affecting the turnover rate and function of cell-type-specific transcripts. In this review, we summarize epigenetic and epitranscriptomic regulatory mechanisms that control the temporal competence of RGCs during mammalian corticogenesis. Furthermore, we discuss various developmental elements that also dynamically regulate the temporal competence of RGCs, including biochemical reaction speed, local environ-mental changes, and subcellular organelle remodeling. Finally, we discuss the underlying mechanisms that regulate the interspecies developmental tempo contributing to human-specific features of brain development.

Automated summary

Radial glial cells (RGCs) are primary neural stem cells in the mammalian cortex, and they give rise to different types of neurons and glial cells with precise spatio-temporal development. Epigenetic and epitranscriptomic regulatory mechanisms, including DNA methylation, histone modifications, and chromatin architecture, play crucial roles in controlling the temporal competence of RGCs during mammalian corticogenesis. Various developmental elements, such as biochemical reaction speed, local environmental changes, and subcellular organelle remodeling, also dynamically regulate the temporal competence of RGCs. Additionally, the underlying mechanisms regulating interspecies developmental tempo contribute to human-specific features of brain development.