Neural Cell News Volume 11.17 | May 3 2017

TOP STORY

Polyglutamine Tracts Regulate Beclin 1-Dependent Autophagy

Scientists showed that the polyglutamine domain enables wild-type ataxin 3 to interact with beclin 1, a key initiator of autophagy. This interaction allowed the deubiquitinase activity of ataxin 3 to protect beclin 1 from proteasome-mediated degradation and thereby enabled autophagy. Starvation-induced autophagy, which is regulated by beclin 1, was particularly inhibited in ataxin-3-depleted human cell lines and mouse primary neurons, and in vivo in mice. [Nature] Abstract

(Ranked by impact factor of the journal)

Multicluster Pcdh Diversity Is Required for Mouse Olfactory Neural Circuit Assembly

The vertebrate clustered protocadherin (Pcdh) cell surface proteins are encoded by three closely linked gene clusters (Pcdhα, Pcdhβ, and Pcdhγ). Researchers showed that all three gene clusters functionally cooperate to provide individual mouse olfactory sensory neurons with the cell surface diversity required for their assembly into distinct glomeruli in the olfactory bulb. Although deletion of individual Pcdh clusters had subtle phenotypic consequences, the loss of all three clusters led to a severe axonal arborization defect and loss of self-avoidance. [Science] Abstract | Press Release

Pcdhαc2 Is Required for Axonal Tiling and Assembly of Serotonergic Circuitries in Mice

Scientists showed that conditional deletion of the mouse protocadherin α (Pcdhα) gene cluster in serotonergic neurons disrupts local axonal tiling and global assembly of serotonergic circuitries and results in depression-like behaviors. Genetic dissection and expression profiling revealed that this role is specifically mediated by Pcdhαc2, which is the only Pcdhα isoform expressed in serotonergic neurons. [Science] Abstract | Press Release

Shh-Mediated Centrosomal Recruitment of PKA Promotes Symmetric Proliferative Neuroepithelial Cell Division

Researchers showed that activation of sonic hedgehog (Shh)/Gli signaling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions. Shh signaling upregulated the expression of pericentrin, which is required to dock PKA to the centrosomes, which in turn exerted a positive feedback onto Shh signaling. [Nat Cell Biol] Abstract | Press Release

A Gene Regulatory Network Balances Neural and Mesoderm Specification during Vertebrate Trunk Development

Investigators used single-cell transcriptomics to identify the molecular signature of neuromesodermal progenitors (NMPs) and reverse engineer the mechanism that regulates their differentiation. Together with genetic perturbations, this revealed a transcriptional network that integrates opposing retinoic acid and Wnt signals to determine the rate at which cells enter and exit the NMP state. [Dev Cell] Full Article | Graphical Abstract

Identification of miRNA-7 by Genome-Wide Analysis as a Critical Sensitizer for TRAIL-Induced Apoptosis in Glioblastoma Cells

The authors found that the expression pattern of microRNA (miR)-7 is closely correlated with sensitivity of glioblastoma (GBM) cells to TNF-related apoptosis-inducing ligand (TRAIL). Their gain and loss of function experiments showed that miR-7 is a potential sensitizer for TRAIL-induced apoptosis in GBM cells. [Nucleic Acids Res] Full Article

Secretagogin Is Expressed by Developing Neocortical GABAergic Neurons in Humans but not Mice and Increases Neurite Arbor Size and Complexity

Through integrative gene coexpression analysis, investigators determined a consensus transcriptional profile of GABAergic neurons in mid-gestation human neocortex. They showed that the calcium-binding protein secretagogin is robustly expressed by neocortical GABAergic neurons derived from caudal ganglionic eminences and lateral ganglionic eminences during human but not mouse brain development. [Cereb Cortex] Abstract

Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations

Scientists showed that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents in midbrain neurons differentiated from induced pluripotent stem cells of Parkinson’s disease (PD) patients with parkin mutations, but not normal subjects. Overexpression of wild-type parkin, but not its PD-causing mutant, abolished the oscillatory activities in patient neurons. [Cell Rep] Full Article | Press Release | Graphical Abstract

Complement C5aR1 Signaling Promotes Polarization and Proliferation of Embryonic Neural Progenitor Cells through PKCζ

Investigators demonstrated polarized expression of C5aR1 on the apical surface of mouse embryonic neural progenitor cells in vivo, and on human embryonic stem cell derived neural progenitors. They showed that signaling of endogenous C5a during mouse embryogenesis drives proliferation of neural progenitor cells within the ventricular zone, and was required for normal brain histogenesis. [J Neurosci] Abstract

Differential Roles for Akt and mTORC1 in the Hypertrophy of Pten Mutant Neurons, a Cellular Model of Brain Overgrowth Disorders

Researchers established forebrain excitatory neuron-specific Pten-deficient cultures as an in vitro model of brain overgrowth disorders, and investigated the effects of this Pten mutation on PI3K/Akt/mTOR signaling and neuronal growth. Mutant neurons exhibited excessive PI3K/Akt/mTOR signaling activity, enlarged somas and increased dendritic arborization. [Neuroscience] Abstract | Graphical Abstract

Intersection of Diverse Neuronal Genomes and Neuropsychiatric Disease: The Brain Somatic Mosaicism Network

The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders. [Science] Abstract | Graphical Abstract

Old and New Challenges in Parkinson’s Disease Therapeutics

Researchers provide an overview of Parkinson’s disease (PD) related therapies and major breakthroughs achieved within this field. They start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. [Prog Neurobiol] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

Novocure™ Announces Data Presentations

Novocure announced that ten data presentations investigating the use of Tumor Treating Fields for the treatment of glioblastoma will be presented. [Press release from Novocure discussing research to be presented at the 5^th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies (WFNOS), Zurich] Press Release

Treatment Completed for All Patients in Parkinson’s Trial

Living Cell Technologies Limited has completed treatment of all six patients in the third and final group of patients in the Phase IIb clinical trial of NTCELL^® for Parkinson’s disease. [Living Cell Technologies Limited] Press Release

NEUROTROPE Announces Positive Top-Line Results from Phase II Study of Bryostatin-1 for Moderate to Severe Alzheimer’s Disease

Neurotrope, Inc. announced positive top-line results from its Phase II study of Bryostatin-1 in patients with moderate to severe Alzheimer’s disease (AD), a population not commonly targeted in AD clinical trials. [Neurotrope, Inc. (PR Newswire Association LLC.)] Press Release

NIH to Limit the Amount of Grant Money a Scientist Can Receive

For the first time, the US National Institutes of Health (NIH) will restrict the amount of funding that an individual scientist can hold at any one time, based on a new point system. The move is part of an ongoing effort to make obtaining grants easier for early and mid-career scientists, who face much tougher odds than their more-experienced colleagues. [Nature News] Editorial

Researchers Frustrated by Italian Misconduct Probe

More than five years ago, Italian police began investigating allegations of research misconduct in papers by Alfredo Fusco, a prominent cancer scientist in Naples. Researchers frustrated by the case’s slow progress have told Nature that there is strong evidence that dozens of papers may contain manipulated data — and that a commercial photography studio was called in to cut and paste images. They say they are speaking out about the magnitude of the allegations because of their increasing impatience with the slow pace of investigations by police and by academic authorities. [Nature News] Editorial

How Science Fares in the U.S. Budget Deal

Congress has finally reached a deal on spending bills for the 2017 fiscal year. House of Representatives and Senate leaders announced that they expect lawmakers to vote on an agreement that wraps together all 12 appropriations bills that fund federal operations. For the past seven months, the government has been operating under a continuing resolution that froze 2017 spending at most agencies at 2016 levels and generally prevented them from starting new programs. [ScienceInsider] Editorial

Controversial UK Research Reform Crosses Finish Line

A controversial and wide-ranging shake-up of the United Kingdom’s (UK’s) research and higher-education landscape has been completed, amid a huge rush by the country’s parliament to push through legislation. [Nature News] Editorial

NEW ISSCR Annual Meeting 2017
June 14-17, 2017
Boston, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Scientist – Cell Biology (Medical Research Council)

NEW Postdoctoral Position – Molecular Biology (KU Leuven)

Career Position – Neural Aging (University of Innsbruck)

Postdoctoral Researcher – Neuroscience and Imaging (Howard Hughes Medical Institute)

Director – BrainHub (Carnegie Mellon University)

Postdoctoral Position(s) – Developmental Neurobiology (Children’s National Health Systems)

Postdoctoral Position(s) – Visual Neuroscience (Yale University)

Postdoctoral Fellow – Spinal Cord Injury Repair (Burke Medical Research Institute Cornell)

Postdoctoral Fellow/Experienced Scientist – Stem Cells and Epigenetics (University of Michigan)

Assistant/Associate Professor – Canada Research Chair in Mental Health (University of Alberta)

Postdoctoral Research Associate – Developmental Neuroscience (University of Nebraska Medical Center)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Neural Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.