Neural Cell News Volume 6.50 | Dec 19 2012

MEK Inhibition Exhibits Efficacy in Human and Mouse Neurofibromatosis Tumors
Researchers used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK signaling contributes to neurofibroma growth in a neurofibromatosis mouse model or in neurofibromatosis type 1 patient malignant peripheral nerve sheath tumors cell xenografts. [J Clin Invest] Full Article | Press Release

Mesenchymal High-Grade Glioma Is Maintained by the ID-RAP1 Axis
ID proteins are master regulators of stemness and anchorage to the extracellular niche microenvironment, suggesting that they may play a role in maintaining glioma-initiating cells. Investigators modeled the probable therapeutic impact of ID inactivation in high grade gliomas (HGG) by selective ablation of Id in tumor cells and after tumor initiation in a new mouse model of human mesenchymal HGG. [J Clin Invest] Full Article

Detection of a-Synuclein Amyloidogenic Aggregates In Vitro and in Cells using Light-Switching Dipyridophenazine Ruthenium(II) Complexes
Investigators demonstrated the use of dipyridophenazine ruthenium(II) to monitor a-synuclein (aS) fibril formation in real-time and to detect and quantify aS aggregates in neuroglioma cells, thereby providing a novel molecular tool to study protein deposition diseases in vitro and in vivo. [J Am Chem Soc] Abstract | Press Release

Activation of 5-HT2A Receptors Upregulates the Function of the Neuronal K-Cl Cotransporter KCC2
Scientists showed that activation of 5-hydroxytryptamine type 2A (5-HT2A) receptors to serotonin hyperpolarizes the reversal potential of inhibitory postsynaptic potentials, in spinal motoneurons, increases the cell membrane expression of KCC2 and both restores endogenous inhibition and reduces spasticity after spinal cord injury in rats. [Proc Natl Acad Sci USA] Abstract

MDGAs Interact Selectively with Neuroligin-2 but Not Other Neuroligins to Regulate Inhibitory Synapse Development
Researchers demonstrated that MDGAs specifically and with a nanomolar affinity bind to neuroligin-2, a cell-adhesion molecule of inhibitory synapses, but do not bind detectably to neuroligin-1 or neuroligin-3. They observed no cell adhesion between cells expressing neuroligin-2 and MDGA1, suggesting a cis interaction. [Proc Natl Acad Sci USA] Abstract

Developmentally Coordinated Extrinsic Signals Drive Human Pluripotent Stem Cell Differentiation toward Authentic DARPP-32⁺ Medium-Sized Spiny Neurons
Using knowledge of human developmental biology and exposure to key neurodevelopmental molecules, human pluripotent stem cells were induced to differentiate into medium-sized spiny neurons. In a feeder-free adherent culture, ventral telencephalic specification is induced by BMP/TGFß inhibition and subsequent SHH/DKK1 treatment. [Development] Abstract

MicroRNA 218 Acts as a Tumor Suppressor by Targeting Multiple Cancer Phenotype Associated Genes in Medulloblastoma
The regulation and function of microRNA 218 (miR-218), which is significantly under-expressed in medulloblastoma, was evaluated. Re-expression of miR-218 resulted in a significant decrease in medulloblastoma cell growth, cell colony formation, cell migration, invasion and tumor sphere size. [J Biol Chem] Abstract | Full Article

Intrinsic Migratory Properties of Cultured Schwann Cells Based on Single-Cell Migration Assay
Based on time-lapse imaging of single isolated Schwann cells, researchers examined the intrinsic migratory properties of Schwann cells and the molecular cytoskeletal machinery of soma translocation during migration. They found that cultured Schwann cells displayed three motile phenotypes, which could transform into each other spontaneously during their migration. [PLoS One] Full Article

In Vitro Comparison of Hypericin and 5-Aminolevulinic Acid-Derived Protoporphyrin IX for Photodynamic Inactivation of Medulloblastoma Cells
In three medulloblastoma cell lines the time- and concentration-dependent intracellular accumulation of Hypericin (HYP) and 5-Aminolevulinic Acid-Derived Protoporphyrin IX (5-ALA-derived PpIX) was analyzed by fluorescence microscopy and FACS. [PLoS One] Full Article

Networks of Polarized Actin Filaments in the Axon Initial Segment Provide a Mechanism for Sorting Axonal and Dendritic Proteins
Using correlative light and scanning electron microscopy, investigators visualized networks of actin filaments several microns wide within the axon initial segment of cortical neurons in culture. [Cell Reports]
Abstract | Graphical Abstract

New Spin on an Old Transition: Epithelial Parallels in Neuronal Adhesion Control
Scientists examined the parallels between the mechanisms controlling epithelial morphogenesis and the cell adhesion events by which neural cells organize germinal zone niches and direct neuronal migration. They focused on the emerging relationship between neuronal adhesive interactions and conserved cell-polarity signaling cascades. [Trends Neurosci] Abstract

Neurons Die in Alzheimer’s Disease because of Faulty Cell Cycle Control, before the Appearance of Plaques and Tangles
Using mouse neurons grown in culture, the researchers found that Aβ oligomers, which are small aggregates of just a few Aβ molecules each, induce the neurons to re-enter the cell cycle. The mechanism for this misplaced re-entry into the cell cycle requires that Aβ oligomers activate multiple protein kinase enzymes, each of which must then attach a phosphate to a specific site on the tau protein. [Press release from The American Society for Cell Biology discussing research presented at 52^nd Annual Meeting, San Francisco] Press Release

A Rare but Lethal Disease in Children, Giant Axonal Neuropathy, Is Tracked to a Failure to Degrade Intermediate Filaments in the Cytoskeleton
Because it is not possible to study nerve cells experimentally from patients, the researchers made use of the observation that other classes of intermediate filaments (IF) are also altered in giant axonal neuropathy (GAN) patients. In particular, the IF vimentin expressed in fibroblasts of children with GAN also forms abnormally large aggregates. In the fibroblasts cultured from GAN patients, the complex network of vimentin filaments and abnormal aggregates disappeared. [Press release from The American Society for Cell Biology discussing research presented at 52^nd Annual Meeting, San Francisco] Press Release

Neural Stem Cell Institute Recommended for $10.6 Million Clinical Trial Grant
The Regenerative Research Foundation (RRF) has been recommended for a grant of $10.6 million by the Funding Committee of the Empire State Stem Cell Board and the NYS stem cell program, NYSTEM. The award would be divided with $5.8 going to the RRF and $4.8 distributed to the other members of the Retinal Stem Cell Consortium over a four year period to enable them to take Neural Stem Cell Institute’s discovery of the RetinalPigment Epithelium Stem Cell to clinical trial for Age-Related Macular Degeneration. [Neural Stem Cell Institute] Press Release
 
Genervon Established that It’s Targeted Drug Benefits ALS Disorder through 8 Pathways and Modulates Over 30 Specific ALS Genes Dynamically
Genervon scientists have confirmed that the target of GM604 regulates over 4,000 genes. More significantly, it modifies ALS progression by modulating at least 30 significant ALS related genes. [Genervon Biopharmaceuticals LLC] Press Release

Cedars-Sinai Physician-Scientist Awarded $3 Million to Study the Most Common Inherited Neurological Disorder
A Cedars-Sinai physician-scientist has been awarded a $3 million grant from the California Institute for Regenerative Medicine to study with new stem cell technology Charcot-Marie-Tooth disease. The researchers will employ induced pluripotent stem cells (iPSCs) created at the Regenerative Medicine Institute, which conducts stem cell research and produces stem cells for study at other institutions through its iPSC Core Facility. [Cedars-Sinai] Press Release

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Research Technologist – Cell Separation (STEMCELL Technologies, Inc.)

Scientist – Endothelial Cell Research (STEMCELL Technologies, Inc.)

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

Product Quality Scientist (STEMCELL Technologies, Inc.)

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

Postdoctoral Position – Neurobiology (Weizmann Institute of Science)

Postdoctoral Position(s) – Cell Biology, Biophysics and Neurobiology (University of Missouri, Kansas City)

Postdoctoral Position – Systems Biology, Neurodegenerative Diseases (The Microsoft Research-University of Trento (COSBI))

Research Fellow – Pediatric Brain Tumor Research (The Hospital for Sick Children, Toronto)

Postdoctoral Position – Transcriptional Regulation in Neural Stem Cells (Washington University School of Medicine)

Faculty Position – Neural Stem Cell Biology (University of Colorado School of Medicine)

Postdoctoral Fellow – Neural Stem Cells and Neurogenesis (University of Texas Southwestern Medical Center at Dallas)

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