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Inhibition of Foxp4 Disrupts Cadherin-based Adhesion of radial glial cells,Leading to Abnormal Differentiation and Migration of Cortical Neurons in Mice

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Neuroscience Bulletin 2023年第7期39卷 1131-1145页

作者： Xue Li Shimin Zou Xiaomeng Tu Shishuai Hao Tian Jiang Jie-Guang Chen School of Ophthalmology and Optometry and Eye Hospital Wenzhou Medical UniversityWenzhou 325027China State Key Laboratory of Optometry Ophthalmology and Vision Scienceand Zhejiang Provincial Key Laboratory of Optometry and OphthalmologyWenzhou 325027China Research Center for Translational Medicine the Afliated Wenling Hospital of Wenzhou Medical UniversityWenling 317500China

Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders(NDDs)that exhibit delayed speech development,intellectual disability,and congenital *** etiology of NDDs is *** we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells(RGCs),respectively,in the mouse neocortex during early *** or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone(VZ).Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating *** ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in *** data indicate that Foxp4 is essential for N-cadherin-based adherens junctions,the loss of which leads to periventricular *** hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.

关键词： Neurogenesis radial migration radial glial cell Ventricular zone N-cadherin

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Developmental Origins of Human Cortical Oligodendrocytes and Astrocytes

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Neuroscience Bulletin 2022年第1期38卷 47-68页

作者： Lin Yang Zhenmeiyu Li Guoping Liu Xiaosu Li Zhengang Yang State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain ScienceInstitute for Translational Brain Researchand Department of NeurologyZhongshan HospitalFudan UniversityShanghai200032China

Human cortical radial glial cells are primary neural stem cells that give rise to cortical glutaminergic projection pyramidal neurons, glial cells (oligodendrocytes and astrocytes) and olfactory bulb GABAergic interneurons. One of prominent features of the human cortex is enriched with glial cells, but there are major gaps in understanding how these glial cells are generated. Herein, by integrating analysis of published human cortical single-cell RNA-Seq datasets with our immunohistochemistical analyses, we show that around gestational week 18, EGFR-expressing human cortical truncated radial glial cells (tRGs) give rise to basal multipotent intermediate progenitors (bMIPCs) that express EGFR, ASCL1, OLIG2 and OLIG1. These bMIPCs undergo several rounds of mitosis and generate cortical oligodendrocytes, astrocytes and olfactory bulb interneurons. We also characterized molecular features of the cortical tRG. Integration of our findings suggests a general picture of the lineage progression of cortical radial glial cells, a fundamental process of the developing human cerebral cortex.

关键词： radial glial cell Intermediate progenitor cell EGFR HOPX Oligodendrocyte Astrocyte Olfactory bulb interneuron Cerebral cortex Human

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Neuronal stem cells in the central nervous system and in human diseases

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Protein & cell 2012年第4期3卷 262-270页

作者： Qian Wu Xiaoqun Wang State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

The process of cortical expansion in the central nerv-ous system is a key step of mammalian brain devel-opment to ensure its physiological *** glial(RG)cells are a glial cell type contributing to this pro-gress as intermediate neural progenitor cells responsi-ble for an increase in the number of cortical *** this review,we discuss the current understanding of RG cells during neurogenesis and provide further in-formation on the mechanisms of neurodevelopmental diseases and stem cell-related brain *** of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these dis-eases.

关键词： radial glial cell neuronal stem cell tumori-genesis glioma

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Epigenetic control on cell fate choice in neural stem cells

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Protein & cell 2012年第4期3卷 278-290页

作者： Xiao-Ling Hu Yuping Wang Qin Shen Center for Stem cell Biology and Regenerative Medicine School of MedicineTsinghua Center for Life SciencesTsinghua UniversityBeijing 100084China Department of Pharmacy Tianjin Children’s HospitalTianjin 300074China

Derived from neural stem cells(NSCs)and progenitor cells originated from the neuroectoderm,the nervous system presents an unprecedented degree of cellular diversity,interwoven to ensure correct connections for propagating information and responding to environ-mental *** and progenitor cells must integrate cell-intrinsic programs and environmental cues to achieve production of appropriate types of neurons and glia at appropriate times and places during *** developmental dynamics are reflected in changes in gene expression,which is regulated by transcription factors and at the epigenetic *** early commitment of neural lineage to functional plas-ticity in terminal differentiated neurons,epigenetic regulation is involved in every step of neural *** we focus on the recent advance in our un-derstanding of epigenetic regulation on orderly genera-tion of diverse neural cell types in the mammalian nervous system,an important aspect of neural devel-opment and regenerative medicine.

关键词： neural stem cells(NSCs) epigenetic regu-lation neurogenesis gliogenesis radial glial cell cerebral cortex subventricular zone(SVZ) DNA methylation histone modification

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Decoding Cortical glial cell Development

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Neuroscience Bulletin 2021年第4期37卷 440-460页

作者： Xiaosu Li Guoping Liu Lin Yang Zhenmeiyu Li Zhuangzhi Zhang Zhejun Xu Yuqun Cai Heng Du Zihao Su Ziwu Wang Yangyang Duan Haotian Chen Zicong Shang Yan You Qi Zhang Miao He Bin Chen Zhengang Yang State Key Laboratory of Medical Neurobiology Institutes of Brain ScienceMOE Frontiers Center for Brain ScienceDepartment of NeurologyInstitute for Translational Brain ResearchZhongshan HospitalFudan UniversityShanghai 200032China Department of Molecular Cell and Developmental BiologyUniversity of California Santa CruzSanta CruzCA 95064USA

Mouse cortical radial glial cells(RGCs)are primary neural stem cells that give rise to cortical oligodendrocytes,astrocytes,and olfactory bulb(OB)GABAergic interneurons in late *** are fundamental gaps in understanding how these diverse cell subtypes are ***,by combining single-cell RNA-Seq with intersectional lineage analyses,we show that beginning at around E16.5,neocortical RGCs start to generate ASCL1^(+)EGFR^(+)apical multipotent intermediate progenitors(MIPCs),which then differentiate into basal MIPCs that express ASCL1,EGFR,OLIG2,and *** basal MIPCs undergo several rounds of divisions to generate most of the cortical oligodendrocytes and astrocytes and a subpopulation of OB ***,single-cell ATAC-Seq supported our model for the genetic logic underlying the specification and differentiation of cortical glial cells and OB *** together,this work reveals the process of cortical radial glial cell lineage progression and the developmental origins of cortical astrocytes and oligodendrocytes.

关键词： radial glial cell Intermediate progenitor cell ASCL1 EGFR OLIG2 Oligodendrocyte Astrocyte Olfactory bulb interneuron Cerebral cortex

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