Neural Cell News Volume 7.25 | Jun 26 2013

Combinatorial Temporal Patterning in Progenitors Expands Neural Diversity
Scientists showed that Drosophila intermediate neural progenitors (INPs) sequentially generate distinct neural subtypes, that INPs sequentially express Dichaete, Grainy head and Eyeless transcription factors, and that these transcription factors are required for the production of distinct neural subtypes. [Nature]
Abstract | Press Release

Small Molecule Inhibitors of Aurora-A Induce Proteasomal Degradation of N-Myc in Childhood Neuroblastoma
Although stabilization of N-Myc does not require the catalytic activity of Aurora-A, researchers showed that two Aurora-A inhibitors, MLN8054 and MLN8237, disrupt the Aurora-A/N-Myc complex and promote degradation of N-Myc mediated by the Fbxw7 ubiquitin ligase. Disruption of the Aurora-A/N-Myc complex inhibits N-Myc-dependent transcription, correlating with tumor regression and prolonged survival in a mouse model of MYCN-driven neuroblastoma. [Cancer Cell] Abstract

mSYD1A, a Mammalian Synapse-Defective-1 Protein, Regulates Synaptogenic Signaling and Vesicle Docking
Scientists identified the intracellular mouse Synapse-Defective-1A (mSYD1A) as a regulator of presynaptic function in mice. mSYD1A forms a complex with presynaptic receptor tyrosine phosphatases and controls tethering of synaptic vesicles at synapses. [Neuron] Abstract | Press Release

Individual Oligodendrocytes Have Only a Few Hours in which to Generate New Myelin Sheaths In Vivo
Researchers showed, using live imaging in zebrafish, that oligodendrocytes make new myelin sheaths during a period of just five hours, with regulation of sheath number after this time limited to occasional retractions. They also showed that activation and reduction of Fyn kinase in oligodendrocytes increases and decreases sheath number per cell, respectively. [Dev Cell] Abstract | Graphical Abstract | Full Article

Cell-Type-Specific Profiling of Gene Expression and Chromatin Binding without Cell Isolation: Assaying RNA Pol II Occupancy in Neural Stem Cells
The authors have developed “TaDa,” a technique that enables cell-specific profiling without cell isolation. They showed that TaDa can be used to identify transcribed genes in a cell-type-specific manner with considerable temporal precision, enabling the identification of differential gene expression between neuroblasts and the neuroepithelial cells from which they derive. [Dev Cell]
Abstract | Graphical Abstract | Full Article

Nucleostemin Deletion Reveals an Essential Mechanism that Maintains the Genomic Stability of Stem and Progenitor Cells
In cultured neural stem cells, depletion of nucleostemin triggers replication-dependent DNA damage and perturbs self-renewal, whereas overexpression of nucleostemin shows a protective effect against hydroxyurea-induced DNA damage. [Proc Natl Acad Sci USA] Abstract

Aptamer Identification of Brain Tumor Initiating Cells
Using Cell-Systematic Evolution of Ligands by Exponential Enrichment with positive selection for tumor initiating cells (TICs) and negative selection for non-TICs and human neural progenitor cells researchers identified TIC aptamers that specifically bind to TICs with excellent Kds. These aptamers select and internalize into glioblastoma cells that self-renew, proliferate, and initiate tumors. [Cancer Res] Abstract

Dose-Dependent Neuroprotection of VEGF₁₆₅ in Huntington’s Disease Striatum
Scientists used bidirectional lentiviral transfer vectors to generate in vitro and in vivo models of Huntington’s disease and to test the therapeutic potential of vascular endothelial growth factor 165 (VEGF₁₆₅). Lentiviral-mediated expression of expansion in the huntingtin protein caused cell death and aggregate formation in human neuroblastoma SH-SY5Y and rat primary striatal cultures. [Mol Ther] Abstract

A Proapoptotic Effect of Valproic Acid on Progenitors of Embryonic Stem Cell-Derived Glutamatergic Neurons
Although the neuroprotective or neurodestructive effects of valproic acid (VPA) have been investigated in heterogeneous cell populations, in this study, researchers used homogeneous populations of neural progenitor cells (NPCs) and glutamatergic cortical pyramidal neurons, which were differentiated from embryonic stem (ES) cells. At therapeutic concentrations, VPA had a proapoptotic effect on ES cell-derived NPCs of glutamatergic neurons, but not on their progeny. [Cell Death Dis] Full Article

Non-Invasive Neural Stem Cells Become Invasive In Vitro by Combinatorial FGF2 and BMP4 Signaling
Sox2-positive neural stem cells (NSCs) from the E14.5 rat cortex were non-invasive and showed only limited migration in vitro. In contrast, FGF2-expanded NSCs showed a strong migratory and invasive phenotype in response to the combination of both factors FGF2 and BMP4. [J Cell Sci] Abstract

Yale Research Projects Exploring New Uses for Failed Drugs get NIH Funding
National Center for Advancing Translational Sciences (NCAT) of the National Institutes of Health (NIH) announced that it will fund Alzheimer’s research headed by neurobiologist Stephen Strittmatter and schizophrenia research led by John Krystal, chair of psychiatry. [Yale School of Medicine] Press Release

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