d-Glucuronolactone attenuates para-xylene-induced defects in neuronal development and plasticity in Xenopus tectum in vivo

AbstractThe Regulator of G protein signaling 4 (Rgs4) is a member of the RGS proteins superfamily that modulates the activity of G-protein coupled receptors. It is mainly expressed in the nervous system and is linked to several neuronal signaling pathways; however, its role in neural development in vivo remains inconclusive. Here, we generated and characterized a rgs4 loss of function model (MZrgs4) in zebrafish. MZrgs4 embryos showed motility defects and presented reduced head and eye sizes, reflecting defective motoneurons axon outgrowth and a significant decrease in the number of neurons in the central and peripheral nervous system. Forcing the expression of Rgs4 specifically within motoneurons rescued their early defective outgrowth in MZrgs4 embryos, indicating an autonomous role for Rgs4 in motoneurons. We also analyzed the role of Akt, Erk and mechanistic target of rapamycin (mTOR) signaling cascades and showed a requirement for these pathways in motoneurons axon outgrowth and neuronal development. Drawing on pharmacological and rescue experiments in MZrgs4, we provide evidence that Rgs4 facilitates signaling mediated by Akt, Erk and mTOR in order to drive axon outgrowth in motoneurons and regulate neuronal numbers.

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Regulation of expression of mRNAs encoding the nerve growth factor receptors p75 and trkA in developing sensory neurons

Development ◽

10.1242/dev.119.3.635 ◽

1993 ◽

Vol 119 (3) ◽

pp. 635-648 ◽

Cited By ~ 17

Author(s):

S. Wyatt ◽

A.M. Davies

Keyword(s):

Neuronal Development ◽

Polymerase Chain Reaction Amplification ◽

Mrna Levels ◽

Regulation Of Expression ◽

Trigeminal Neurons ◽

Nerve Growth Factor Receptors ◽

Reaction Amplification ◽

Amplification Technique

We have used a quantitative reverse transcription/polymerase chain reaction amplification technique to study the regulation of p75 mRNA and trkA mRNA expression in developing NGF-dependent trigeminal neurons. Before becoming NGF dependent, these neurons express low levels of p75 and trkA mRNAs in vivo. At this stage in vitro, the level of p75 mRNA is maintained and up-regulated by BDNF, whereas the level of trkA mRNA is sustained independently of neurotrophins and is down-regulated by BDNF. With the acquisition of NGF dependence, p75 and trkA mRNA levels increase markedly in vivo. At this stage in vitro, the level of p75 mRNA is up-regulated by NGF, but this response is lost at later stages. The level of trkA mRNA is sustained in neurons grown with NGF but is not up-regulated by concentrations of NGF above those required to support survival. At no stage during the early development of trigeminal neurons do depolarising levels of potassium ions affect the expression of either p75 mRNA or trkA mRNA. These findings suggest that the expression of p75 and trkA mRNAs are differentially regulated by BDNF and NGF at successive early stages of neuronal development.

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KBP interacts with SCG10, linking Goldberg–Shprintzen syndrome to microtubule dynamics and neuronal differentiation

Human Molecular Genetics ◽

10.1093/hmg/ddq280 ◽

2010 ◽

Vol 19 (18) ◽

pp. 3642-3651 ◽

Cited By ~ 30

Author(s):

Maria M. Alves ◽

Grzegorz Burzynski ◽

Jean-Marie Delalande ◽

Jan Osinga ◽

Annemieke van der Goot ◽

...

Keyword(s):

Nervous System ◽

Enteric Nervous System ◽

Neuronal Differentiation ◽

Cortical Neurons ◽

Neuronal Development ◽

Direct Interaction ◽

Clinical Disorder ◽

Neurite Development

Abstract Goldberg–Shprintzen syndrome (GOSHS) is a rare clinical disorder characterized by central and enteric nervous system defects. This syndrome is caused by inactivating mutations in the Kinesin Binding Protein (KBP) gene, which encodes a protein of which the precise function is largely unclear. We show that KBP expression is up-regulated during neuronal development in mouse cortical neurons. Moreover, KBP-depleted PC12 cells were defective in nerve growth factor-induced differentiation and neurite outgrowth, suggesting that KBP is required for cell differentiation and neurite development. To identify KBP interacting proteins, we performed a yeast two-hybrid screen and found that KBP binds almost exclusively to microtubule associated or related proteins, specifically SCG10 and several kinesins. We confirmed these results by validating KBP interaction with one of these proteins: SCG10, a microtubule destabilizing protein. Zebrafish studies further demonstrated an epistatic interaction between KBP and SCG10 in vivo . To investigate the possibility of direct interaction between KBP and microtubules, we undertook co-localization and in vitro binding assays, but found no evidence of direct binding. Thus, our data indicate that KBP is involved in neuronal differentiation and that the central and enteric nervous system defects seen in GOSHS are likely caused by microtubule-related defects.

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Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

10.1101/2020.12.10.419507 ◽

2020 ◽

Author(s):

Lauren Tereshko ◽

Ya Gao ◽

Brian A. Cary ◽

Gina G. Turrigiano ◽

Piali Sengupta

Keyword(s):

Primary Cilia ◽

Neuronal Development ◽

Pyramidal Neurons ◽

Somatostatin Receptor ◽

Cognitive Disorders ◽

Mammalian Brain ◽

Excitatory Synapses ◽

Ciliary Signaling ◽

Neocortical Pyramidal Neurons

ABSTRACTPrimary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to pyramidal neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

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Regulation of vasculogenesis and angiogenesis by EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells

Blood ◽

10.1182/blood.v100.4.1326.h81602001326_1326_1333 ◽

2002 ◽

Vol 100 (4) ◽

pp. 1326-1333 ◽

Cited By ~ 74

Author(s):

Yuichi Oike ◽

Yasuhiro Ito ◽

Koichi Hamada ◽

Xiu-Qin Zhang ◽

Keishi Miyata ◽

...

Keyword(s):

Endothelial Cells ◽

Tyrosine Kinases ◽

Molecular Mechanisms ◽

Neuronal Development ◽

Receptor Tyrosine Kinases ◽

Vascular Endothelial Cells ◽

Mesenchymal Cells ◽

Ephb Receptor ◽

Vasculogenesis And Angiogenesis

Although the cellular and molecular mechanisms governing angiogenesis are only beginning to be understood, signaling through endothelial-restricted receptors, particularly receptor tyrosine kinases, has been shown to play a pivotal role in these events. Recent reports show that EphB receptor tyrosine kinases and their transmembrane-type ephrin-B2 ligands play essential roles in the embryonic vasculature. These studies suggest that cell-to-cell repellent effects due to bidirectional EphB/ephrin-B2 signaling may be crucial for vascular development, similar to the mechanism described for neuronal development. To test this hypothesis, we disrupted the precise expression pattern of EphB/ephrin-B2 in vivo by generating transgenic (CAGp-ephrin-B2 Tg) mice that express ephrin-B2 under the control of a ubiquitous and constitutive promoter, CMV enhancer-β-actin promoter-β-globin splicing acceptor (CAG). These mice displayed an abnormal segmental arrangement of intersomitic vessels, while such anomalies were not observed in Tie-2p-ephrin-B2 Tg mice in which ephrin-B2 was overexpressed in only vascular endothelial cells (ECs). This finding suggests that non-ECs expressing ephrin-B2 alter the migration of ECs expressing EphB receptors into the intersomitic region where ephrin-B2 expression is normally absent. CAGp-ephrin-B2 Tg mice show sudden death at neonatal stages from aortic dissecting aneurysms due to defective recruitment of vascular smooth muscle cells to the ascending aorta. EphB/ephrin-B2 signaling between endothelial cells and surrounding mesenchymal cells plays an essential role in vasculogenesis, angiogenesis, and vessel maturation.

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Glycogen serves as an energy source that maintains astrocyte cell proliferation in the neonatal telencephalon

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x16665380 ◽

2016 ◽

Vol 37 (6) ◽

pp. 2294-2307 ◽

Cited By ~ 5

Author(s):

Hitoshi Gotoh ◽

Tadashi Nomura ◽

Katsuhiko Ono

Keyword(s):

Energy Source ◽

Cell Proliferation ◽

Glycogen Phosphorylase ◽

Cell Cycle Progression ◽

Neuronal Development ◽

Kinase Inhibitors ◽

Primary Cultures ◽

Glycogen Metabolism ◽

Radial Glial Cells

Large amounts of energy are required when cells undergo cell proliferation and differentiation for mammalian neuronal development. Early neonatal mice face transient starvation and use stored energy for survival or to support development. Glycogen is a branched polysaccharide that is formed by glucose, and serves as an astrocytic energy store for rapid energy requirements. Although it is present in radial glial cells and astrocytes, the role of glycogen during development remains unclear. In the present study, we demonstrated that glycogen accumulated in glutamate aspartate transporter (GLAST)+ astrocytes in the subventricular zone and rostral migratory stream. Glycogen levels markedly decreased after birth due to the increase of glycogen phosphorylase, an essential enzyme for glycogen metabolism. In primary cultures and in vivo, the inhibition of glycogen phosphorylase decreased the proliferation of astrocytic cells. The number of cells in the G1 phase increased in combination with the up-regulation of cyclin-dependent kinase inhibitors or down-regulation of the phosphorylation of retinoblastoma protein (pRB), a determinant for cell cycle progression. These results suggest that glycogen accumulates in astrocytes located in specific areas during the prenatal stage and is used as an energy source to maintain normal development in the early postnatal stage.

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Microtubule-dependent ribosome localization in C. elegans neurons

eLife ◽

10.7554/elife.26376 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 16

Author(s):

Kentaro Noma ◽

Alexandr Goncharov ◽

Mark H Ellisman ◽

Yishi Jin

Keyword(s):

Cell Biology ◽

Neuronal Development ◽

Ultrastructural Level ◽

Synthesis Methods ◽

Tissue Specific ◽

C Elegans ◽

Multicellular Organisms ◽

Axonal Trafficking ◽

Insight Into

Subcellular localization of ribosomes defines the location and capacity for protein synthesis. Methods for in vivo visualizing ribosomes in multicellular organisms are desirable in mechanistic investigations of the cell biology of ribosome dynamics. Here, we developed an approach using split GFP for tissue-specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes are detected as fluorescent puncta in the axons and synaptic terminals of specific neuron types, correlating with ribosome distribution at the ultrastructural level. We found that axonal ribosomes change localization during neuronal development and after axonal injury. By examining mutants affecting axonal trafficking and performing a forward genetic screen, we showed that the microtubule cytoskeleton and the JIP3 protein UNC-16 exert distinct effects on localization of axonal and somatic ribosomes. Our data demonstrate the utility of tissue-specific visualization of ribosomes in vivo, and provide insight into the mechanisms of active regulation of ribosome localization in neurons.

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In Vivo Time-Lapse Imaging of Neuronal Development inXenopus

Cold Spring Harbor Protocols ◽

10.1101/pdb.top077156 ◽

2013 ◽

Vol 2013 (9) ◽

pp. pdb.top077156 ◽

Cited By ~ 4

Author(s):

Edward S. Ruthazer ◽

Anne Schohl ◽

Neil Schwartz ◽

Aydin Tavakoli ◽

Marc Tremblay ◽

...

Keyword(s):

Neuronal Development ◽

Time Lapse ◽

Time Lapse Imaging

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Drosophila Glia: Models for Human Neurodevelopmental and Neurodegenerative Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms21144859 ◽

2020 ◽

Vol 21 (14) ◽

pp. 4859

Author(s):

Taejoon Kim ◽

Bokyeong Song ◽

Im-Soon Lee

Keyword(s):

Nervous System ◽

Neurodegenerative Disorders ◽

Brain Function ◽

Cell Biology ◽

Disease Susceptibility ◽

Neuronal Development ◽

In Vivo Model ◽

Health And Disease ◽

Drosophila Models

Glial cells are key players in the proper formation and maintenance of the nervous system, thus contributing to neuronal health and disease in humans. However, little is known about the molecular pathways that govern glia–neuron communications in the diseased brain. Drosophila provides a useful in vivo model to explore the conserved molecular details of glial cell biology and their contributions to brain function and disease susceptibility. Herein, we review recent studies that explore glial functions in normal neuronal development, along with Drosophila models that seek to identify the pathological implications of glial defects in the context of various central nervous system disorders.

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Interleukin-6 and interleukin-11: same same but different

Biological Chemistry ◽

10.1515/hsz-2013-0166 ◽

2013 ◽

Vol 394 (9) ◽

pp. 1145-1161 ◽

Cited By ~ 73

Author(s):

Christoph Garbers ◽

Jürgen Scheller

Keyword(s):

Neuronal Development ◽

Inflammatory Diseases ◽

Janus Kinase ◽

Mitogen Activated Protein Kinase ◽

Cytokine Signaling ◽

Downstream Signaling ◽

Mitogen Activated Protein ◽

Β Receptor ◽

Redundant Functions

Abstract The pleiotropic physiological functions of interleukin (IL-)6 type cytokines range from embryonic development and tissue homoeostasis to neuronal development and T cell differentiation. In contrast, imbalance of the well-controlled cytokine signaling network leads to chronic inflammatory diseases and cancer. IL-6 and IL-11 both signal through a homodimer of the ubiquitously expressed β-receptor glycoprotein 130 (gp130). Specificity is gained through an individual IL-6/IL-11 α-receptor, which does not directly participate in signal transduction, although the initial cytokine binding event to the α-receptor leads to the final complex formation with the β-receptors. Both cytokines activate the same downstream signaling pathways, which are predominantly the mitogen-activated protein kinase (MAPK)-cascade and the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway. However, recent studies have highlighted divergent roles of the two related cytokines. Here, we will discuss how the biochemical similarities are translated into unique and non-redundant functions of IL-6 and IL-11 in vivo and illustrate strategies for cytokine-specific therapeutic intervention.

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