Abnormal Development of Forebrain Midline Glia and Commissural Projections in<i>Nfia</i>Knock-Out Mice

Shu, Tianzhi; Butz, Kenneth G.; Plachez, Céline; Gronostajski, Richard M.; Richards, Linda J.

doi:10.1523/jneurosci.23-01-00203.2003

Cited by 207 publications

(255 citation statements)

References 54 publications

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“…At D24, pTEL progenitor clusters expressed slightly higher levels of MKI67 and GPC3, indicating these early populations are mitotically active (Filmus, 2001;Scholzen and Gerdes, 2000). By D54 and D100, pTEL progenitor clusters express NFIA and HOPX, consistent with a transition to astrogliogenesis and/or outer radial glial cell production (Deneen et al, 2006;Pollen et al, 2015;Shu et al, 2003;Thomsen et al, 2016). After D54, pMGE clusters also express higher levels of HOPX, in addition to AQP4, S100B, ANXA1, and S100A10 compared to earlier clusters.…”

Section: Scrna-seq Analysis Of In Vitro-derived Human Interneuronsmentioning

confidence: 86%

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Close¹,

Yao²,

Miller³

et al. 2017

Neuron

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SummaryGABAergic interneurons are essential for neural circuit function and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and ultimately therapeutic cell replacement. We describe here a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation timecourse of cell types using single-cell RNAseq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late. By comparing the transcriptomes of immature interneurons to more mature neurons, we identified genes important for human interneuron differentiation. Many of these genes were previously implicated in neurodevelopmental and neuropsychiatric disorders. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access

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Section: Scrna-seq Analysis Of In Vitro-derived Human Interneuronsmentioning

confidence: 86%

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Close¹,

Yao²,

Miller³

et al. 2017

Neuron

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show abstract

“…Recently, NFia, NFib, and NFic genes have been disrupted in mice. NFia knock-out mice are characterized by dramatic neuroanatomical defects, whereas NFib is needed for both brain development and lung maturation (35,36). In contrast, disruption of NFic causes postnatal loss of molar roots (37).…”

Section: Discussionmentioning

confidence: 99%

Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the α1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes

Gopalan

Wilczynska

Konik

et al. 2006

Journal of Biological Chemistry

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Discrete tissue-specific changes in chromatin structure of the distal serpin subcluster on human chromosome 14q32.1 allow a single gene encoding ␣ 1 -antichymotrypsin (ACT) to be expressed in astrocytes and glioma cells. This astrocyte-specific regulation involves activatory protein-1 (AP-1) because overexpression of dominantnegative c-jun(TAM67) abolishes ACT expression in glioma cells. Here we identify a new regulatory element, located within the ؊13-kb enhancer of the ACT gene, that binds nuclear factor-1 (NFI) and is indispensable for the full basal transcriptional activity of the ACT gene. Furthermore, down-regulation of NFI expression by siRNA abolishes basal ACT expression in glioma cells. However, NFI does not mediate astrocyte-specific expression by itself, but likely cooperates with AP-1. A detailed analysis of the 14-kb long 5-flanking region of the ACT gene indicated the presence of adjacent NFI and AP-1 elements that colocalized with DNase I-hypersensitive sites found in astrocytes and glioma cells. Interestingly, knock-down of NFI expression also specifically abrogates the expression of glial acidic fibrillary protein (GFAP), which is an astrocyte-specific marker protein. Mutations introduced into putative NFI and AP-1 elements within the 5-flanking region of the GFAP gene also diminished basal expression of the reporter. In addition, we found, using isoform-specific siRNAs, that NFI-X regulates the astrocytespecific expression of ACT and GFAP. We propose that NFI-X cooperates with AP-1 by an unknown mechanism in astrocytes, which results in the expression of a subset of astrocyte-specific genes.2 is expressed at low levels by astrocytes in the brain under normal physiological conditions. However, elevated ACT levels have been observed in several neuropathological disorders of the central nervous system, including Alzheimer disease (1, 2). This drastic change in ACT expression is caused by proinflammatory cytokines, including IL-1, IL-6, oncostatin M (OSM), and tumor necrosis factor (TNF)␣, which are released at the site of tissue damage (3, 4). ACT secreted by reactive astrocytes subsequently associates with the ␤-amyloid peptide, which is the major component of pathological deposits found in the brains of Alzheimer disease patients (1).ACT belongs to the serine protease inhibitor (serpin) family of proteins and is also expressed in the liver and secreted into the plasma (5). The gene encoding ACT is clustered with 10 additional serpin genes on human chromosome 14q32.1 and resides within the distal serpin subcluster that also contains genes encoding kallistatin, protein C inhibitor, and the kallistatin-like protein (6, 7). The expression profile of the distal serpin subcluster is dramatically different between astrocytes and hepatocytes. All four genes are expressed in hepatocytes, whereas only the ACT gene is expressed in astrocytes (8). Investigations of the regulatory mechanisms controlling the selective expression of ACT in astrocytes and glioma cells demonstrated that the ACT gene is localize...

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“…An additional mechanism of guidance at the cortical midline occurs via transient neuronal populations that form the subcallosal sling and a cellular corridor for callosal axons to cross the midline (Shu et al, 2003b;Niquille et al, 2009). We stained sections from both KOs and WT littermates with antibodies against the transcription factor Nfia, which labels the subcallosal sling (Shu et al, 2003a) and found it to be intact in both Slc12a6…”

Section: ⌬18/⌬18mentioning

confidence: 99%

Loss of Neuronal Potassium/Chloride Cotransporter 3 (KCC3) Is Responsible for the Degenerative Phenotype in a Conditional Mouse Model of Hereditary Motor and Sensory Neuropathy Associated with Agenesis of the Corpus Callosum

Shekarabi

Moldrich²,

Rasheed³

et al. 2012

J. Neurosci.

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Disruption of the potassium/chloride cotransporter 3 (KCC3), encoded by the SLC12A6 gene, causes hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and neurodegenerative disorder affecting both the peripheral nervous system and CNS. However, the precise role of KCC3 in the maintenance of ion homeostasis in the nervous system and the pathogenic mechanisms leading to HMSN/ACC remain unclear. We established two Slc12a6 Cre/LoxP transgenic mouse lines expressing C-terminal truncated KCC3 in either a neuron-specific or ubiquitous fashion. Our results suggest that neuronal KCC3 expression is crucial for axon volume control. We also demonstrate that the neuropathic features of HMSN/ACC are predominantly due to a neuronal KCC3 deficit, while the auditory impairment is due to loss of non-neuronal KCC3 expression. Furthermore, we demonstrate that KCC3 plays an essential role in inflammatory pain pathways. Finally, we observed hypoplasia of the corpus callosum in both mouse mutants and a marked decrease in axonal tracts serving the auditory cortex in only the general deletion mutant. Together, these results establish KCC3 as an important player in both central and peripheral nervous system maintenance.

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Abnormal Development of Forebrain Midline Glia and Commissural Projections inNfiaKnock-Out Mice

Cited by 207 publications

References 54 publications

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Nuclear Factor-1-X Regulates Astrocyte-specific Expression of the α1-Antichymotrypsin and Glial Fibrillary Acidic Protein Genes

Loss of Neuronal Potassium/Chloride Cotransporter 3 (KCC3) Is Responsible for the Degenerative Phenotype in a Conditional Mouse Model of Hereditary Motor and Sensory Neuropathy Associated with Agenesis of the Corpus Callosum

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