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

• 成果类型: Article
• 署名作者: Liang, Xiaoyi G.; Hoang, Kendy; Meyerink, Brandon L.; Pratiksha, Kc; Paraiso, Kitt; Wang, Li; Jones, Ian R.; Zhang, Yue; Katzman, Sol; Finn, Thomas S.; Tsyporin, Jeremiah; Qu, Fangyuan; Chen, Zhaoxu; Visel, Axel; Kriegstein, Arnold; Shen, Yin; Pilaz, Louis - Jan; Chen, Bin
• 署名单位: University of California System; University of California Santa Cruz; Sanford Health; Sanford Health; University of South Dakota; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California Santa Cruz; United States Department of Energy (DOE); Joint Genome Institute - JGI; University of California System; University of California Merced; Zhejiang University; Liangzhu Laboratory; Zhejiang University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10925
• DOI: 10.1073/pnas.2321711121
• 发表日期: 2024-05-14
• 关键词: neocortical projection neurons; white-matter; oligodendrocytes; olig2; astrocytes; progenitor; forebrain; reveals; IMPACT; cells

摘要

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 Olig2 expression are conserved between the mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells. Significance In the developing cerebral cortex, neural stem cells switch from generating cortical excitatory neurons to producing cortical glia and olfactory bulb interneurons. This lineage switch is essential for generating appropriate numbers of neuronal and glial cell types in the cortex and requires the transcription of Olig2 in cortical progenitors. In this study, we describe the identification of multiple enhancers that control the expression of Olig2 in cortical progenitors using ChIP - seq, CUT&RUN, ATAC - seq, enhancer reporter, and deletion mice. Our study reveals a conserved mechanism for Olig2 gene expression and neural stem cell lineage regulation between the mouse and human.