Neural Cell News Volume 7.28 | Jul 17 2013

Developmental Origins of Central Norepinephrine Neuron Diversity
Researchers elucidated the lineal relationship between molecularly distinct progenitor populations in the developing mouse hindbrain and mature norepinephrine neuron subtype identity. They identified four genetically separable subpopulations of mature norepinephrine neurons differing in their anatomical location, axon morphology and efferent projection pattern. [Nat Neurosci] Abstract

Otx2 and Onecut1 Promote the Fates of Cone Photoreceptors and Horizontal Cells and Repress Rod Photoreceptors
Scientists report the identification of a cis-regulatory module (CRM) for the thyroid hormone receptor beta (Thrb) gene, an early cone marker. They found that ThrbCRM1 is active in progenitor cells biased to the production of cones and an interneuronal cell type, the horizontal cell. [Dev Cell] Abstract

Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte-Neuron Communication
Scientists describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. [PLoS Biol] Full Article | Press Release

Dock3 Attenuates Neural Cell Death Due to NMDA Neurotoxicity and Oxidative Stress in a Mouse Model of Normal Tension Glaucoma
Researchers found that dedicator of cytokinesis 3 (Dock3) directly binds to the intracellular C-terminus domain of NR2B, an N-methyl-d-aspartate (NMDA) receptor subunit. In transgenic mice overexpressing Dock3, NR2B expression in the retina was significantly decreased and NMDA-induced retinal degeneration was ameliorated. [Cell Death Differ] Abstract

Intracellular ASIC1a Regulates Mitochondrial Permeability Transition-Dependent Neuronal Death
When challenged with hydrogen peroxide (H₂O₂), ASIC1a^-/- neurons are resistant to cytochrome c release and inner mitochondrial membrane depolarization, suggesting an impairment of mitochondrial permeability transition (MPT) due to ASIC1a deletion. Consistently, H₂O₂-induced neuronal death, which is MPT dependent, is reduced in ASIC1a^-/- neurons. [Cell Death Differ] Abstract

RUNX3 Interacts with MYCN and Facilitates Protein Degradation in Neuroblastoma
Researchers report that high levels of RUNX3 expression contribute to the favorable outcome in patients with neuroblastoma, whereas low levels of RUNX3 expression result in poor outcome. Exogenous expression of RUNX3 strongly inhibits cell proliferation and migration in neuroblastoma cell lines. [Oncogene] Abstract

Tumor Suppressor Nf2 Limits Expansion of the Neural Progenitor Pool by Inhibiting Yap/Taz Transcriptional Coactivators
Researchers showed that the tumor suppressor neurofibromatosis 2 (Nf2) limits the expansion of neural progenitor cells (NPCs) in the mammalian dorsal telencephalon. Nf2 is localized at the apical region of NPCs. In the absence of Nf2, NPCs of the cortical hem, hippocampal primordium and neocortical primordium overexpand, while production of Cajal-Retzius cells and hippocampal neurons decreases, resulting in severe malformation of the hippocampus in adult mice. [Development] Abstract

Caspase Blockade Induces RIP3-Mediated Programmed Necrosis in Toll-Like Receptor-Activated Microglia
Investigators report that microglia activated through Toll-like receptors undergo RIP1/RIP3-dependent programmed necrosis (necroptosis) when exposed to the pan caspase inhibitor zVAD-fmk. [Cell Death Dis] Full Article

Temporal Control of Retroviral Transgene Expression in Newborn Cells in the Adult Brain
Besides classical transgenesis-based approaches, retrovirus-mediated genetic manipulation is frequently used to study mechanisms that regulate neurogenesis in the nervous system. Investigators showed that fusion of a tamoxifen-regulatable estrogen receptor (ER^T2) motif to transcription factors enables temporal control of transgene expression in adult mouse neural stem/progenitor cells in vitro and in vivo. [Stem Cell Rep] Abstract | Graphical Abstract | Full Article

Wnt/ß-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina
Researchers showed that upon activation of Wnt/ß-catenin signaling, mouse retinal neurons can be transiently reprogrammed in vivo back to a precursor stage. This occurs after their spontaneous fusion with transplanted hematopoietic stem and progenitor cells. Moreover, they demonstrate that retinal damage is essential for cell-hybrid formation in vivo. [Cell Rep] Abstract | Graphical Abstract | Full Article | Press Release

Utilization of Neural Stem Cell-Derived Models to Study Anesthesia-Related Toxicity and Preventative Approaches
The authors focus on how embryonic neural stem cells, when combined with biochemical, pathological, and pharmacokinetic assessments, might serve as a bridging platform to provide the most expeditious approaches toward decreasing the uncertainty in extrapolating preclinical data to the human condition. They present key concepts in stem cell biology with respect to the nervous system, present an overview of neural development, and summarize the involvement of neural cell types in developmental neurotoxicity associated with anesthetic exposure. [Mol Neurobiol] Abstract

Dental Stem Cells and Their Promising Role in Neural Regeneration: An Update
Each dental stem cell population possesses specific characteristics and advantages, which are summarized in this review. Furthermore, the neural characteristics of dental pulp stem cells and their potential role in (peripheral) neural regeneration are discussed. [Clin Oral Invest] Abstract

Phase II Clinical Data Show Statistically Significant Improvement for Lu AE58054 as Add-On to Donepezil, versus Donepezil Alone, on Cognitive Symptoms of Alzheimer’s Disease
H. Lundbeck A/S and Otsuka Pharmaceutical Co., Ltd. announced the presentation of the first clinical data on the investigational drug Lu AE58054 in Alzheimer’s disease. The phase II clinical study demonstrated that treatment with Lu AE58054 as add-on to donepezil for six months improved cognitive performance in patients with moderate Alzheimer’s disease. [Press release from H. Lundbeck A/S discussing research presented at the Alzheimer’s Association International Conference 2013, Boston] Press Release

From our sponsor:
Free wallchart from Nature Neuroscience – Neural Stem Cells. Request your copy.

Alkermes Announces Initiation of Phase II Clinical Study of ALKS 3831, Designed to Be a Broad Spectrum Oral Antipsychotic for the Treatment of Schizophrenia
Alkermes plc announced the initiation of a phase II study of ALKS 3831, a novel oral atypical antipsychotic drug candidate designed to be a broad spectrum treatment for schizophrenia. The double-blind, active-controlled, dose-ranging study in approximately 400 patients with schizophrenia will assess ALKS 3831, a proprietary combination of a novel opioid modulator, ALKS 33, and olanzapine, an approved atypical antipsychotic medicine, compared to olanzapine alone. [Alkermes plc] Press Release

Auspex Initiates Phase III Trial of SD-809 in Huntington’s Disease
Auspex Pharmaceuticals announced that the first patient has been enrolled in a multi-center Phase III pivotal trial of its lead investigational drug, SD-809 for the treatment of involuntary movements associated with Huntington’s Disease. [Auspex Pharmaceuticals] Press Release

Access to Clinical Data and Biospecimens, and Funding to Use Them, from The Michael J. Fox Foundation Encourages Drug Development
The Michael J. Fox Foundation for Parkinson’s Research has announced that qualified researchers may now request access to clinical data and biospecimens from a collection of studies exploring promising areas in Parkinson’s research. The Foundation is also offering funding for use and analysis of the available information and materials to progress therapeutic and disease-modifying treatments. [PR Newswire Association LLC] Press Release