A conserved molecular logic for neurogenesis to gliogenesis switch in the cerebral cortex

作者：Xiaoyi G. Liang, Kendy Hoang, Brandon L. Meyerink, Pratiksha KC, Kitt Paraiso, Li Wang, Ian Rees Jones, Yue Zhang, Sol Katzman, Thomas S. Finn, Jeremiah Tsyporin, Fangyuan Qu, Zhaoxu Chen, Axel Visel, Arnold R. Kriegstein, Yin Shen, Louis‐Jan Pilaz, Bin Chen · 发表于：Proceedings of the National Academy of Sciences · 年份：2024 · DOI：10.1073/pnas.2321711121 · 被引用次数：18 · 研究领域：Neurogenesis and neuroplasticity mechanisms、Hedgehog Signaling Pathway Studies、Epigenetics and DNA Methylation

During development, neural stem cells in the cerebral cortex, also known as radial glial cells (RGCs), generate excitatory neurons, followed by production of cortical macroglia and inhibitory neurons that migrate to the olfactory bulb (OB). Understanding the mechanisms for this lineage switch is fundamental for unraveling how proper numbers of diverse neuronal and glial cell types are controlled. We and others recently showed that Sonic Hedgehog (Shh) signaling promotes the cortical RGC lineage switch to generate cortical oligodendrocytes and OB interneurons. During this process, cortical RGCs generate intermediate progenitor cells that express critical gliogenesis genes Ascl1 , Egfr, and Olig2 . The increased Ascl1 expression and appearance of Egfr + and Olig2 + cortical progenitors are concurrent with the switch from excitatory neurogenesis to gliogenesis and OB interneuron neurogenesis in the cortex. While Shh signaling promotes Olig2 expression in the developing spinal cord, the exact mechanism for this transcriptional regulation is not known. Furthermore, the transcriptional regulation of Olig2 and Egfr has not been explored. Here, we show that in cortical progenitor cells, multiple regulatory programs, including Pax6 and Gli3, prevent precocious expression of Olig2 , a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating ...