NOTCH, ERK, and SHH signaling respectively control the fate determination of cortical glia and olfactory bulb interneurons
Abstract
During cortical development, radial glial cells (neural stem cells) initially are neurogenic, generating intermediate progenitor cells that exclusively produce glutamatergic pyramidal neurons. Next, radial glial cells generate tripotential intermediate progenitor cells (Tri-IPCs) that give rise to cortical astrocytes and oligodendrocytes, and olfactory bulb interneurons. The molecular mechanisms underlying the transition from cortical neurogenesis to gliogenesis, and the subsequent fate determination of cortical astrocytes, oligodendrocytes, and olfactory bulb interneurons, remain unclear. Here, we report that extracellular signal-regulated kinase (ERK) signaling plays a fundamental role in promoting cortical gliogenesis and the generation of Tri-IPCs. Additionally, sonic hedgehog-smoothened-glioma-associated oncogene homolog (SHH-SMO-GLI) activator signaling has an auxiliary function to ERK during these processes. We further demonstrate that, from Tri-IPCs, NOTCH signaling is crucial for the fate determination of astrocytes, while ERK signaling plays a prominent role in oligodendrocyte fate specification, and SHH signaling is required for the fate determination of olfactory bulb interneurons. We provide evidence suggesting that this mechanism is conserved in both mice and humans. Finally, we propose a unifying principle of mammalian cortical gliogenesis.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (21)
Yanjing Gao
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, Qianjin Street 2699, Changchun 130012, P. R. China
Mengge Sun
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Tongye Fu
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Ziwu Wang
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Xin Jiang
Lin Yang
Xiaoyi G. Liang
Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz
Guoping Liu
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Yu Tian
Feihong Yang
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Jialin Li
Zhenmeiyu Li
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Xiaosu Li
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Yan You
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Chaoqiong Ding
Department of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University
Yuan Wang
Tong Ma
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Zhuangzhi Zhang
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Zhejun Xu
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University
Bin Chen
Zhengang Yang
Department of Neurology, Zhongshan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University