Decoding Cortical Glial Cell Development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE161132 | GEO | 2021/02/05
REPOSITORIES: GEO
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Project description:During development neural stem cells (NSCs) 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 Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is 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. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-06 | GSE254692 | GEO
Project description:During development neural stem cells (NSCs) 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 Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is 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. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-02 | GSE254690 | GEO
Project description:During development neural stem cells (NSCs) 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 Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is 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. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-06 | GSE254691 | GEO
Project description:During development neural stem cells (NSCs) 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 Shh signaling promotes cortical RGCs to switch lineage to generate cortical oligodendrocytes and OB interneurons. During this lineage switch, cortical RGCs generate intermediate progenitor cells (IPCs) that express Ascl1, Egfr and Olig2, genes critically regulating gliogenesis. The timing of increased Ascl1 expression and the appearance of Egfr+ and Olig2+ cortical progenitors is 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. Further, the transcriptional regulation of Olig2 and Egfr has not been explored. Here we show that in cortical progenitor cells, multiple genetic programs, including Pax6 and Gli3, prevent precocious expression of Olig2, a gene essential for production of cortical oligodendrocytes and astrocytes. We identify multiple distal enhancers that control Olig2 expression in cortical progenitors and show that the mechanisms for regulating Olig2 expression are conserved between mouse and human. Our study reveals evolutionarily conserved regulatory logic controlling the lineage switch of cortical neural stem cells.
2024-05-06 | GSE254689 | GEO
Project description:During cortical development, radial glial cells, known as neural stem cells, initially generate a large number of cortical glutamatergic pyramidal neurons through a process called neurogenesis. This is followed by the generation of a diversity of cortical astrocytes, oligodendrocytes, and olfactory bulb interneurons, known as gliogenesis. However, the molecular mechanisms underlying the switch 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 cortical glial progenitors. Additionally, SHH-SMO-GLI activator signaling has an auxiliary function to ERK during these processes. We further demonstrate that NOTCH signaling is absolutely required for the fate determination of astrocytes, while ERK signaling plays a prominent role in oligodendrocyte fate specification, and SHH signaling is crucial for the fate determination of olfactory bulb interneurons from cortical progenitors. We provide evidence suggesting that this mechanism is conserved in both mice and humans. Finally, we propose a unifying principle of mammalian cortical gliogenesis.
2024-08-23 | GSE274547 | GEO
Project description:During cortical development, radial glial cells, known as neural stem cells, initially generate a large number of cortical glutamatergic pyramidal neurons through a process called neurogenesis. This is followed by the generation of a diversity of cortical astrocytes, oligodendrocytes, and olfactory bulb interneurons, known as gliogenesis. However, the molecular mechanisms underlying the switch 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 cortical glial progenitors. Additionally, SHH-SMO-GLI activator signaling has an auxiliary function to ERK during these processes. We further demonstrate that NOTCH signaling is absolutely required for the fate determination of astrocytes, while ERK signaling plays a prominent role in oligodendrocyte fate specification, and SHH signaling is crucial for the fate determination of olfactory bulb interneurons from cortical progenitors. We provide evidence suggesting that this mechanism is conserved in both mice and humans. Finally, we propose a unifying principle of mammalian cortical gliogenesis.
2024-08-21 | GSE275004 | GEO
Project description:Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2F/- mice), GSX2+ and ASCL1+ neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1 and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development. This SuperSeries is composed of the SubSeries listed below.
2019-01-24 | GSE121215 | GEO
Project description:In the cerebral cortex, projection neurons and interneurons work coordinately to establish functional neural networks and to control the balance between excitatory versus inhibitory synaptic activities for normal cortical functions. While the specific mechanisms that control productions of projection neurons and interneurons are beginning to be revealed, a global characterization of the molecular differences between these two groups of neurons is in need for a more comprehensive understanding of their developmental specifications as well as their cortical functions. Previous studies have shown that the majority of cortical projection neurons are produced by radial glial cells (RGCs) through intermediate progenitor cells (IPCs) which can be marked by the expression of transcription factor Tbr2(Eomes). In this study, taking advantage of lineage tracing power of combining Tbr2(Eomes)-GFP and DCX-mRFP transgenic reporter mice, we prospectively separated IPC-derived neurons (IPNs) from non-IPC-derived neurons (non-IPNs) of the embryonic cortex. Molecular characterizations revealed that IPNs and non-IPNs were enriched with projection neurons and interneurons, respectively. Transcriptome analyses documented distinct groups of genes differentially expressed between these two groups of neurons. These data present a useful resource for further investigation of the molecular regulations and functions of projection neurons and interneurons.
2015-08-12 | GSE62042 | GEO
Project description:In the mammalian brain, Notch signaling maintains the cortical stem cell pool and regulates the glial cell fate choice and differentiation. However, the function of Notch in regulating glial development and its involvement in tumorigenesis have not been well understood. Here, we show that Notch inactivation by genetic deletion of Rbpj in stem cells decreases astrocytes but increases oligodendrocytes with altered internal states. Interestingly, inhibiting Notch in glial progenitors does not affect cell generation but instead accelerates the growth of Notch-deprived oligodendrocyte progenitor cells (OPCs), and OPC-related glioma. We also identified a crosstalk between oligodendrocytes and astrocytes, with premyelinating oligodendrocytes secreting Bmp4, which is repressed by Notch, to upregulate GFAP expression in adjacent astrocytes. Moreover, Notch inactivation in stem cells causes a glioma subtype shift from astroglia-associated to OPC-correlated patterns, and vice versa. Our study reveals Notch's context-dependent function, promoting astrocytes and astroglia-associated glioma in stem cells and repressing OPCs and related glioma in glial progenitors.
2023-08-12 | GSE240223 | GEO
Project description:In the mammalian brain, Notch signaling maintains the cortical stem cell pool and regulates the glial cell fate choice and differentiation. However, the function of Notch in regulating glial development and its involvement in tumorigenesis have not been well understood. Here, we show that Notch inactivation by genetic deletion of Rbpj in stem cells decreases astrocytes but increases oligodendrocytes with altered internal states. Interestingly, inhibiting Notch in glial progenitors does not affect cell generation but instead accelerates the growth of Notch-deprived oligodendrocyte progenitor cells (OPCs), and OPC-related glioma. We also identified a crosstalk between oligodendrocytes and astrocytes, with premyelinating oligodendrocytes secreting Bmp4, which is repressed by Notch, to upregulate GFAP expression in adjacent astrocytes. Moreover, Notch inactivation in stem cells causes a glioma subtype shift from astroglia-associated to OPC-correlated patterns, and vice versa. Our study reveals Notch's context-dependent function, promoting astrocytes and astroglia-associated glioma in stem cells and repressing OPCs and related glioma in glial progenitors.
2023-08-12 | GSE240222 | GEO