Neural Cell News Volume 7.12 | Mar 27 2013

Smurf2-Mediated Degradation of EZH2 Enhances Neuron Differentiation and Improves Functional Recovery after Ischaemic Stroke
Scientists identified Smurf2 as the E3 ubiquitin ligase responsible for the polyubiquitination and proteasome-mediated degradation of EZH2, which is required for neuron differentiation. A ChIP-on-chip screen combined with gene microarray analysis revealed that PPARγ was the only gene involved in neuron differentiation with significant changes in both its modification and expression status during differentiation. [EMBO Mol Med] Abstract | Full Article

Generation of Induced Neurons via Direct Conversion In Vivo
Researchers showed that transplanted human fibroblasts and human astrocytes, which are engineered to express inducible forms of neural reprogramming genes, convert into neurons when reprogramming genes are activated after transplantation. [Proc Natl Acad Sci USA] Full Article | Press Release

Hunger-Promoting Hypothalamic Neurons Modulate Effector and Regulatory T-Cell Responses
Researchers showed that selective knockdown of Sirtuin 1 in hypothalamic Agouti-related peptide-expressing neurons, which renders these cells less responsive to cues of low energy availability, significantly promotes CD4⁺ T-cell activation by increasing production of T helper 1 and 17 proinflammatory cytokines via mediation of the sympathetic nervous system. [Proc Natl Acad Sci USA] Abstract

Impaired Endolysosomal Function Disrupts Notch Signaling in Optic Nerve Astrocytes
Scientists showed that loss of βA3/A1-crystallin in astrocytes does not impede Notch ligand binding or extracellular cleavages. However, it affects vacuolar-type proton ATPase activity, thereby compromising acidification of the endolysosomal compartments, leading to reduced γ-secretase-mediated processing and release of the Notch intracellular domain. [Nat Comm] Abstract

Centaurin-α1-Ras-Elk-1 Signaling at Mitochondria Mediates β-Amyloid-Induced Synaptic Dysfunction
Scientists report that β-amyloid peptide transiently increases the expression level of centaurin-α1 in neurons, which induces a Ras-dependent association of Elk-1 with mitochondria, leading to mitochondrial and synaptic dysfunction in organotypic hippocampal slices of rats. [J Neurosci] Abstract | Press Release

Snail Depletes the Tumorigenic Potential of Glioblastoma
Investigators showed that bone morphogenetic protein signaling induces Smad-dependent expression of the transcriptional regulator Snail in a rapid and sustained manner. Consistent with its already established promigratory function in other cell types, they report that Snail silencing decreases glioblastoma multiforme cell migration. [Oncogene] Full Article

Functional Impacts of NRXN1 Knockdown on Neurodevelopment in Stem Cell Models
Investigators used human induced pluripotent stem cells and human embryonic stem cells as models to investigate the functional impacts of NRXN1 knockdown. They first generated human induced pluripotent stem cells from skin fibroblasts and differentiated them into neural stem cells. [PLoS One] Full Article

Sox10-Dependent Neural Crest Origin of Olfactory Microvillous Neurons in Zebrafish
Using photoconversion-based fate mapping and live cell tracking coupled with laser ablation, scientists followed neural crest precursors as they migrated from the neural tube to the nasal cavity. A subset that coexpressed Sox10 protein and a neurogenin1 reporter ingressed into the olfactory epithelium and differentiated into microvillous sensory neurons. [eLife] Full Article

Nanotopography-Mediated Reverse Uptake for siRNA Delivery into Neural Stem Cells to Enhance Neuronal Differentiation
Scientists developed a nanotopography-mediated reverse uptake delivery platform to demonstrate a simple and efficient technique for delivering siRNA into neural stem cells. [Sci Rep] Full Article

Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants
Researchers uncovered a mechanism for axon guidance by demonstrating that axons can accurately navigate in the absence of a Netrin gradient if apoptotic signaling is blocked. Deletion of the two Drosophila NetA and NetB genes leads to guidance defects and increased apoptosis, and expression of either gene at the midline is sufficient to rescue the connectivity defects and cell death. [Cell Rep]
Abstract | Graphical Abstract | Video Abstract | Press Release

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Fattah Neuroscience Initiative Advances with President’s Signature
The Fattah Neuroscience Initiative, which is designed to make game-changing progress in the understanding of and therapies for brain development, cognition, disease and injury, has achieved a significant new accomplishment as President Obama signed legislation to engage the private sector more fully in brain science and therapy development. [US House of Representatives] Press Release

Lundbeck and Otsuka Further Expand Alliance and Enter into Collaboration for the Development and Commercialization of Lu AE58054 in Development for Alzheimer’s Disease
H. Lundbeck A/S and Otsuka Pharmaceutical Co., Ltd. announced a license and development agreement for Lu AE58054, a selective 5HT6 receptor antagonist currently in development for the treatment of Alzheimer’s disease. [Otsuka Pharmaceutical Co., Ltd.] Press Release

Neuralstem Secures $8 Million in Debt Financing from Hercules
Neuralstem, Inc. announced that it secured $8 million in debt financing with Hercules Technology Growth Capital, to fund the company’s capital budget through late 2014. [PR Newswire Association LLC.]
Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

Postdoctoral Position – Neurobiology (Weizmann Institute of Science)

Postdoctoral Fellow – Neural Stem Cells and Neurogenesis (UT Southwestern Medical Center)

Lecturer or Reader – Associate Professor (University of Reading)

Postdoctoral Position – Adult Neurogenesis and Neural Survival Signaling (University of Kentucky)

Postdoctoral Fellow – Regulation of Gliomagenesis (UT Southwestern Medical Center at Dallas)

PhD Opportunity (University of East Anglia)

Chief Laboratory Scientist – Cell Culture Specialist (Axol Bioscience Ltd)

Director – Centre of Developmental Neurobiology (King’s College London)

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