EZH2 Is Essential for Fate Determination in the Mammalian Isthmic Area.

Abstract:

:The polycomb group proteins (PcGs) are a group of epigenetic factors associated with gene silencing. They are found in several families of multiprotein complexes, including polycomb repressive complex 2 (PRC2). EZH2, EED and SUZ12 form the core components of the PRC2 complex, which is responsible for the mono, di- and trimethylation of lysine 27 of histone 3 (H3K27Me3), the chromatin mark associated with gene silencing. Loss-of-function studies of Ezh2, the catalytic subunit of PRC2, have shown that PRC2 plays a role in regulating developmental transitions of neuronal progenitor cells (NPCs); from self-renewal to differentiation and the neurogenic-to-gliogenic fate switch. To further address the function of EZH2 and H3K27me3 during neuronal development, we generated a conditional mutant in which Ezh2 was removed in the mammalian isthmic (mid-hindbrain) region from E10.5 onward. Loss of Ezh2 changed the molecular coding of the anterior ventral hindbrain leading to a fate switch and the appearance of ectopic dopaminergic (DA) neurons. The correct specification of the isthmic region is dependent on the signaling factors produced by the Isthmic organizer (IsO), located at the border of the mid- and hindbrain. We propose that the change of cellular fate is a result of the presence of Otx2 in the hindbrain of Ezh2 conditional knock-outs (cKOs) and a dysfunctional IsO, as represented by the loss of Fgf8 and Wnt1. Our work implies that next to controlling developmental transitions, EZH2 mediated gene silencing is important for specification of the isthmic region by influencing IsO functioning and repressing Otx2 in the hindbrain.

journal_name

Front Mol Neurosci

authors

Wever I,Wagemans CMRJ,Smidt MP

doi

10.3389/fnmol.2019.00076

subject

Has Abstract

pub_date

2019-04-09 00:00:00

pages

76

issn

1662-5099

journal_volume

12

pub_type

杂志文章
  • Conditional Loss of Hoxa5 Function Early after Birth Impacts on Expression of Genes with Synaptic Function.

    abstract::Hoxa5 is a member of the Hox gene family that plays critical roles in successive steps of the central nervous system formation during embryonic and fetal development. In the mouse, Hoxa5 was recently shown to be expressed in the medulla oblongata and the pons from fetal stages to adulthood. In these territories, Hoxa5...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00369

    authors: Lizen B,Moens C,Mouheiche J,Sacré T,Ahn MT,Jeannotte L,Salti A,Gofflot F

    更新日期:2017-11-15 00:00:00

  • CB1 and LPA1 Receptors Relationship in the Mouse Central Nervous System.

    abstract::Neurolipids are a class of bioactive lipids that are produced locally through specific biosynthetic pathways in response to extracellular stimuli. Neurolipids are important endogenous regulators of neural cell proliferation, differentiation, oxidative stress, inflammation and apoptosis. Endocannabinoids (eCBs) and lys...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2019.00223

    authors: González de San Román E,Manuel I,Ledent C,Chun J,Rodríguez de Fonseca F,Estivill-Torrús G,Santín LJ,Rodríguez Puertas R

    更新日期:2019-09-19 00:00:00

  • Subsynaptic Domains in Super-Resolution Microscopy: The Treachery of Images.

    abstract::The application of super-resolution optical microscopy to investigating synaptic structures has revealed a highly heterogeneous and variable intra-synaptic organization. Dense subsynaptic protein assemblies named subsynaptic domains or SSDs have been proposed as structural units that regulate the efficacy of neuronal ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2019.00161

    authors: Yang X,Specht CG

    更新日期:2019-07-02 00:00:00

  • Dynamic Regulation of the Adenosine Kinase Gene during Early Postnatal Brain Development and Maturation.

    abstract::The ubiquitous metabolic intermediary and nucleoside adenosine is a "master regulator" in all living systems. Under baseline conditions adenosine kinase (ADK) is the primary enzyme for the metabolic clearance of adenosine. By regulating the availability of adenosine, ADK is a critical upstream regulator of complex hom...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2016.00099

    authors: Kiese K,Jablonski J,Boison D,Kobow K

    更新日期:2016-10-20 00:00:00

  • A Novel Microtubule-Binding Drug Attenuates and Reverses Protein Aggregation in Animal Models of Alzheimer's Disease.

    abstract::Age-progressive neurodegenerative pathologies, including Alzheimer's disease (AD), are distinguished and diagnosed by disease-specific components of intra- or extra-cellular aggregates. Increasing evidence suggests that neuroinflammation promotes protein aggregation, and is involved in the etiology of neurological dis...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2019.00310

    authors: Kakraba S,Ayyadevara S,Penthala NR,Balasubramaniam M,Ganne A,Liu L,Alla R,Bommagani SB,Barger SW,Griffin WST,Crooks PA,Shmookler Reis RJ

    更新日期:2019-12-12 00:00:00

  • Achaete-Scute Homolog 1 Expression Controls Cellular Differentiation of Neuroblastoma.

    abstract::Neuroblastoma, the major cause of infant cancer deaths, results from fast proliferation of undifferentiated neuroblasts. Treatment of high-risk neuroblastoma includes differentiation with retinoic acid (RA); however, the resistance of many of these tumors to RA-induced differentiation poses a considerable challenge. H...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2016.00156

    authors: Kasim M,Heß V,Scholz H,Persson PB,Fähling M

    更新日期:2016-12-21 00:00:00

  • Metabotropic Glutamate Receptor 7: A New Therapeutic Target in Neurodevelopmental Disorders.

    abstract::Neurodevelopmental disorders (NDDs) are characterized by a wide range of symptoms including delayed speech, intellectual disability, motor dysfunction, social deficits, breathing problems, structural abnormalities, and epilepsy. Unfortunately, current treatment strategies are limited and innovative new approaches are ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2018.00387

    authors: Fisher NM,Seto M,Lindsley CW,Niswender CM

    更新日期:2018-10-23 00:00:00

  • Deep Survey of GABAergic Interneurons: Emerging Insights From Gene-Isoform Transcriptomics.

    abstract::GABAergic interneuron diversity is a key feature in the brain that helps to create different brain activity patterns and behavioral states. Cell type classification schemes-based on anatomical, physiological and molecular features-have provided us with a detailed understanding of the distinct types that constitute thi...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2019.00115

    authors: Que L,Winterer J,Földy C

    更新日期:2019-05-07 00:00:00

  • Mouse Panx1 Is Dispensable for Hearing Acquisition and Auditory Function.

    abstract::Panx1 forms plasma membrane channels in brain and several other organs, including the inner ear. Biophysical properties, activation mechanisms and modulators of Panx1 channels have been characterized in detail, however the impact of Panx1 on auditory function is unclear due to conflicts in published results. To addres...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00379

    authors: Zorzi V,Paciello F,Ziraldo G,Peres C,Mazzarda F,Nardin C,Pasquini M,Chiani F,Raspa M,Scavizzi F,Carrer A,Crispino G,Ciubotaru CD,Monyer H,Fetoni AR,M Salvatore A,Mammano F

    更新日期:2017-11-28 00:00:00

  • LRP1 Modulates APP Intraneuronal Transport and Processing in Its Monomeric and Dimeric State.

    abstract::The low-density lipoprotein receptor-related protein 1, LRP1, interacts with APP and affects its processing. This is assumed to be mostly caused by the impact of LRP1 on APP endocytosis. More recently, also an interaction of APP and LRP1 early in the secretory pathway was reported whereat retention of LRP1 in the ER l...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00118

    authors: Herr UM,Strecker P,Storck SE,Thomas C,Rabiej V,Junker A,Schilling S,Schmidt N,Dowds CM,Eggert S,Pietrzik CU,Kins S

    更新日期:2017-04-27 00:00:00

  • Memory Training Program Decreases the Circulating Level of Cortisol and Pro-inflammatory Cytokines in Healthy Older Adults.

    abstract::Aging cognitive decline has been associated to impairment of the Hypothalamus Pituitary Adrenals (HPA) axis activity and a higher level of the systemic inflammation. However, little is known about the molecules driving this process at peripheral level. In addition, the cognitive function is to some extent modifiable w...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00233

    authors: Pesce M,Tatangelo R,La Fratta I,Rizzuto A,Campagna G,Turli C,Ferrone A,Franceschelli S,Speranza L,Verrocchio MC,De Lutiis MA,Felaco M,Grilli A

    更新日期:2017-07-24 00:00:00

  • Pin1 Binding to Phosphorylated PSD-95 Regulates the Number of Functional Excitatory Synapses.

    abstract::The post-synaptic density protein 95 (PSD-95) plays a central role in excitatory synapse development and synaptic plasticity. Phosphorylation of the N-terminus of PSD-95 at threonine 19 (T19) and serine 25 (S25) decreases PSD-95 stability at synapses; however, a molecular mechanism linking PSD-95 phosphorylation to al...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2020.00010

    authors: Delgado JY,Nall D,Selvin PR

    更新日期:2020-03-13 00:00:00

  • Tunneling Nanotubes and Gap Junctions-Their Role in Long-Range Intercellular Communication during Development, Health, and Disease Conditions.

    abstract::Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions, exosomes and recently described...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00333

    authors: Ariazi J,Benowitz A,De Biasi V,Den Boer ML,Cherqui S,Cui H,Douillet N,Eugenin EA,Favre D,Goodman S,Gousset K,Hanein D,Israel DI,Kimura S,Kirkpatrick RB,Kuhn N,Jeong C,Lou E,Mailliard R,Maio S,Okafo G,Osswald M,

    更新日期:2017-10-17 00:00:00

  • An Insight into the Increasing Role of LncRNAs in the Pathogenesis of Gliomas.

    abstract::Long non-coding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of gliomas are not fully understood. With the development of deep sequencing analyses, an extensive...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00053

    authors: Yan Y,Xu Z,Li Z,Sun L,Gong Z

    更新日期:2017-02-28 00:00:00

  • Homeostasis of the Intraparenchymal-Blood Glutamate Concentration Gradient: Maintenance, Imbalance, and Regulation.

    abstract::It is widely accepted that glutamate is the most important excitatory neurotransmitter in the central nervous system (CNS). However, there is also a large amount of glutamate in the blood. Generally, the concentration gradient of glutamate between intraparenchymal and blood environments is stable. However, this gradie...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00400

    authors: Bai W,Zhou YG

    更新日期:2017-12-05 00:00:00

  • Screening the Molecular Framework Underlying Local Dendritic mRNA Translation.

    abstract::In the last decade, bioinformatic analyses of high-throughput proteomics and transcriptomics data have enabled researchers to gain insight into the molecular networks that may underlie lasting changes in synaptic efficacy. Development and utilization of these techniques have advanced the field of learning and memory s...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00045

    authors: Namjoshi SV,Raab-Graham KF

    更新日期:2017-02-24 00:00:00

  • Stable STIM1 Knockdown in Self-Renewing Human Neural Precursors Promotes Premature Neural Differentiation.

    abstract::Ca2+ signaling plays a significant role in the development of the vertebrate nervous system where it regulates neurite growth as well as synapse and neurotransmitter specification. Elucidating the role of Ca2+ signaling in mammalian neuronal development has been largely restricted to either small animal models or prim...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2018.00178

    authors: Gopurappilly R,Deb BK,Chakraborty P,Hasan G

    更新日期:2018-06-11 00:00:00

  • From Neural Tube Formation Through the Differentiation of Spinal Cord Neurons: Ion Channels in Action During Neural Development.

    abstract::Ion channels are expressed throughout nervous system development. The type and diversity of conductances and gating mechanisms vary at different developmental stages and with the progressive maturational status of neural cells. The variety of ion channels allows for distinct signaling mechanisms in developing neural c...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2020.00062

    authors: Goyal R,Spencer KA,Borodinsky LN

    更新日期:2020-04-24 00:00:00

  • The Coordinated Action of Calcineurin and Cathepsin D Protects Against α-Synuclein Toxicity.

    abstract::The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological proc...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00207

    authors: Aufschnaiter A,Habernig L,Kohler V,Diessl J,Carmona-Gutierrez D,Eisenberg T,Keller W,Büttner S

    更新日期:2017-06-30 00:00:00

  • Corrigendum: Gap Junctions in A8 Amacrine Cells Are Made of Connexin36 but Are Differently Regulated Than Gap Junctions in AII Amacrine Cells.

    abstract::[This corrects the article DOI: 10.3389/fnmol.2019.00099.]. ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,已发布勘误

    doi:10.3389/fnmol.2019.00149

    authors: Yadav SC,Tetenborg S,Dedek K

    更新日期:2019-06-12 00:00:00

  • Altered Organization of GABA(A) Receptor mRNA Expression in the Depressed Suicide Brain.

    abstract::Inter-relationships ordinarily exist between mRNA expression of GABA(A) subunits in the frontopolar cortex (FPC) of individuals that had died suddenly from causes other than suicide. However, these correlations were largely absent in persons that had died by suicide. In the present investigation, these findings were e...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/neuro.02.003.2010

    authors: Poulter MO,Du L,Zhurov V,Palkovits M,Faludi G,Merali Z,Anisman H

    更新日期:2010-03-29 00:00:00

  • Functions of GSK-3 Signaling in Development of the Nervous System.

    abstract::Glycogen synthase kinase-3 (GSK-3) is central to multiple intracellular pathways including those activated by Wnt/β-catenin, Sonic Hedgehog, Notch, growth factor/RTK, and G protein-coupled receptor signals. All of these signals importantly contribute to neural development. Early attention on GSK-3 signaling in neural ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2011.00044

    authors: Kim WY,Snider WD

    更新日期:2011-11-17 00:00:00

  • Epinephrine May Contribute to the Persistence of Traumatic Memories in a Post-traumatic Stress Disorder Animal Model.

    abstract::The importance of catecholamines in post-traumatic stress disorder (PTSD) still needs to be explored. We aimed to evaluate epinephrine's (EPI) causal role and molecular mechanism for the persistence of PTSD traumatic memories. Wild-type (WT) and EPI-deficient mice (phenylethanolamine-N-methyltransferase-knockout mice,...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2020.588802

    authors: Martinho R,Oliveira A,Correia G,Marques M,Seixas R,Serrão P,Moreira-Rodrigues M

    更新日期:2020-10-26 00:00:00

  • Cysteines as Redox Molecular Switches and Targets of Disease.

    abstract::Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2017.00167

    authors: Fra A,Yoboue ED,Sitia R

    更新日期:2017-06-06 00:00:00

  • The Regulatory Role of Long Noncoding RNAs in Different Brain Cell Types Involved in Ischemic Stroke.

    abstract::Stroke results in high morbidity and high mortality worldwide, with ischemic stroke accounting for 80% to 85%. As effective treatments for ischemic stroke remain limited because of the narrow therapeutic time window, a better understanding of the pathologic mechanism and new therapeutic intervention targets are needed...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章,评审

    doi:10.3389/fnmol.2019.00061

    authors: Chen R,Xu X,Huang L,Zhong W,Cui L

    更新日期:2019-03-22 00:00:00

  • Repeated Restraint Stress Led to Cognitive Dysfunction by NMDA Receptor-Mediated Hippocampal CA3 Dendritic Spine Impairments in Juvenile Sprague-Dawley Rats.

    abstract::Although numerous studies have indicated that chronic stress causes cognitive dysfunction with the impairment of synaptic structures and functions, the relationship between cognitive deficits induced by repeated restraint stress and the level of NMDA receptors in the subregion of the hippocampus has been relatively un...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2020.552787

    authors: Sun DS,Zhong G,Cao HX,Hu Y,Hong XY,Li T,Li X,Liu Q,Wang Q,Ke D,Liu GP,Ma RH,Luo DJ

    更新日期:2020-10-19 00:00:00

  • Early history of glycine receptor biology in Mammalian spinal cord circuits.

    abstract::In this review we provide an overview of key in vivo experiments undertaken in the cat spinal cord in the 1950s and 1960s, and point out their contributions to our present understanding of glycine receptor (GlyR) function. Importantly, some of these discoveries were made well before an inhibitory receptor, or its agon...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2010.00013

    authors: Callister RJ,Graham BA

    更新日期:2010-05-21 00:00:00

  • The Inhibitory Effect of α/β-Hydrolase Domain-Containing 6 (ABHD6) on the Surface Targeting of GluA2- and GluA3-Containing AMPA Receptors.

    abstract::The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) are major excitatory receptors that mediate fast neurotransmission in the mammalian brain. The surface expression of functional AMPARs is crucial for synaptic transmission and plasticity. AMPAR auxiliary subunits control ...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00055

    authors: Wei M,Jia M,Zhang J,Yu L,Zhao Y,Chen Y,Ma Y,Zhang W,Shi YS,Zhang C

    更新日期:2017-03-02 00:00:00

  • Alterations in Morphology and Adult Neurogenesis in the Dentate Gyrus of Patched1 Heterozygous Mice.

    abstract::Many genes controlling neuronal development also regulate adult neurogenesis. We investigated in vivo the effect of Sonic hedgehog (Shh) signaling activation on patterning and neurogenesis of the hippocampus and behavior of Patched1 (Ptch1) heterozygous mice (Ptch1+/- ). We demonstrated for the first time, that Ptch1+...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2018.00168

    authors: Antonelli F,Casciati A,Tanori M,Tanno B,Linares-Vidal MV,Serra N,Bellés M,Pannicelli A,Saran A,Pazzaglia S

    更新日期:2018-05-23 00:00:00

  • Neuronal Culture Microenvironments Determine Preferences in Bioenergetic Pathway Use.

    abstract::In the brain, metabolic supply and demand is directly coupled to neuronal activation. Methods for culturing primary rodent brain cells have come of age and are geared toward sophisticated modeling of human brain physiology and pathology. However, the impact of the culture microenvironment on neuronal function is rarel...

    journal_title:Frontiers in molecular neuroscience

    pub_type: 杂志文章

    doi:10.3389/fnmol.2017.00305

    authors: Sünwoldt J,Bosche B,Meisel A,Mergenthaler P

    更新日期:2017-09-29 00:00:00