Spastin Contributes to Neural Development through the Regulation of Microtubule Dynamics in the Primary Cilia of Neural Stem Cells

Jeong, Bohyeon; Kim, So Yeon; Kim, Dae‐Soo; Shin, Won-Ho; Lee, Jae-Ran; Kim, Nam-Soon; Lee, Da Yong

doi:10.1016/j.neuroscience.2019.05.024

Cited by 14 publications

(15 citation statements)

References 37 publications

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“…Cells cultured in well plates were fixed with 4% paraformaldehyde solution (PFA) at room temperature for 20 min and stained as described previously [ 18 ]. Primary antibodies used for staining included anti-NANOG (Invitrogen), anti-OCT4 (Santa Cruz Biotechnology), anti-TRA1-60 (Merck Millipore), anti-TRA1-81 (Merck Millipore), anti-SSEA3 (R&D systems), anti-SSEA4 (R&D systems), anti-NESTIN (abcam), anti-SOX2 (R&D systems,), anti-GATA4 (Santa Cruz Biotechnology), and anti-SMA (Sigma-Aldrich) antibodies.…”

Section: Methodsmentioning

confidence: 99%

Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability

et al. 2021

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Intellectual disability (ID) is a neurodevelopmental disorder defined by below-average intelligence (intelligence quotient of <70) accompanied by adaptive behavior deficits. Defects in the functions of neural stem cells during brain development are closely linked to the pathogenesis of ID. To understand the molecular etiology of ID, we examined neural stem cells from individuals with Duchenne muscular dystrophy (DMD), a genetic disorder in which approximately one-third of the patients exhibit ID. In this study, we generated induced pluripotent stem cells from peripheral blood mononuclear cells from a normal individual and DMD patients with and without ID to identify ID-specific functional and molecular abnormalities. We found defects in neural ectoderm formation in the group of DMD patients with ID. Our transcriptome analysis of patient-derived neural stem cells revealed altered expression of genes related to the hippo signaling pathway and neuroactive ligand-receptor interaction, implicating these in the pathogenesis of ID in patients with DMD.

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Section: Methodsmentioning

confidence: 99%

Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability

et al. 2021

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“…Hippocampal regions were dissected from embryonic (E16.5) mouse brain. Primary hippocampal NSCs were prepared as described previously 33,34 .…”

Section: Culture Of Mouse Hippocampal Nscsmentioning

confidence: 99%

“…Dissociated cells (3,000 cells/well) were seeded into 24-well ultra-low attachment plates with NSC growth medium. After 7-9 days the proliferation rate was measured as previously described 33,34 .…”

Section: Nsc Proliferation Assaymentioning

confidence: 99%

“…Neurospheres treated with vehicle and PSNPs (25 µg/ml) were dissociated into single NSCs followed by plating onto matrigel coated-24 well culture plate (1.5 x 10 5 cells/well) with differentiation medium (DMEM/F12 media, N2, B27, Glutamax) to induce neuronal and glial differentiation. After 7-9 days, the cells were immunolabeled with anti-Tuj1 (1:1,000; Biolegend) and anti-GFAP (1:200; Thermo Fisher Scientific) antibodies for neurons and astrocytes, respectively 33,34 .…”

Section: Multi-lineage Differentiation Assaymentioning

confidence: 99%

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Maternal exposure to polystyrene nanoplastics causes brain abnormalities in progeny

Jeong

Ryu

Baek

et al. 2021

Preprint

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As global plastic production continues to grow, microplastics released from a massive quantity of plastic wastes have become a critical environmental concern. These microplastic particles are found in a wide range of living organisms in a diverse array of ecosystems. In this study, we investigated the biological effects of polystyrene nanoplastics (PSNPs) on development of the central nervous system using cultured neural stem cells (NSCs) and mice exposed to PSNPs during developmental stages. Our study demonstrates that maternal administration of PSNPs during gestation and lactating periods altered the functioning of NSCs, neural cell compositions, and brain histology in progeny. Similarly, our in vitro study also shows PSNP-induced molecular and functional defects in NSCs. Finally, we show that the abnormal brain development caused by exposure to high concentrations of PSNPs results in neurophysiological and cognitive deficits in a gender-specific manner. Our data demonstrate the possibility that exposure to high amounts of PSNPs may increase the risk of neurodevelopmental defects.

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“…Spastin likely serves to coordinately regulate the microtubule cytoskeleton and membrane components (reviewed in Lumb et al, 2012), and although clear consensus is still in progress, several working hypotheses have emerged for its neuronal roles. Potential processes include neural stem cell proliferation (Jeong et al, 2019), remodeling the endoplasmic reticulum and other endomembrane components (e.g., Park et al, 2010;Allison et al, 2019), lipid droplet function (Papadopoulos et al, 2015;Chang et al, 2019), axon regeneration (Stone et al, 2012), axon outgrowth (Wood et al, 2006), axon transport (Tarrade et al, 2006;Kasher et al, 2009), and synaptic morphology and transmission (Sherwood et al, 2004;Trotta et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Suppression of spastin Mutant Phenotypes by Pak3 Loss Implicates a Role for Reactive Glia in AD-HSP

et al. 2020

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Neurodegenerative mechanisms due to mutations in spastin currently center on neuronal defects, primarily in microtubule and endomembrane regulation. Spastin loss in Drosophila larvae compromises neuronal microtubule distribution, alters synaptic bouton morphology, and weakens synaptic transmission at glutamatergic neuromuscular junction (NMJ) synapses. Pak3, a p21-activated kinase that promotes actin polymerization and filopodial projections, is required for these spastin mutant defects; animals lacking both genes have normal NMJs. Here we show that Pak3 is expressed in central and peripheral glial populations, and reduction of Pak3 specifically in subperineurial glial cells is sufficient to suppress the phenotypes associated with spastin loss. Subperineurial glia in the periphery ensheathe motor neuron axons and have been shown to extend actin-based projections that regulate synaptic terminals during normal NMJ development. We find that these subperineurial glial projections are Pak3-dependent and nearly twice as frequent in spastin mutants, while in Pak3, spastin double mutants, neither glial projections nor synaptic defects are observed. Spastin deficiency thus increases Pak3-dependent subperineurial glia activity, which is in turn required for neuronal defects. Our results demonstrate a central role for Pak3-mediated, altered glial behavior in the neuronal defects due to spastin loss, and suggest that a similar reactive glia-mediated mechanism may underlie human AD-HSP pathogenesis.

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Spastin Contributes to Neural Development through the Regulation of Microtubule Dynamics in the Primary Cilia of Neural Stem Cells

Cited by 14 publications

References 37 publications

Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability

Altered Gene Expression Profiles in Neural Stem Cells Derived from Duchenne Muscular Dystrophy Patients with Intellectual Disability

Maternal exposure to polystyrene nanoplastics causes brain abnormalities in progeny

Suppression of spastin Mutant Phenotypes by Pak3 Loss Implicates a Role for Reactive Glia in AD-HSP

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