Neural Cell News Volume 8.20 | May 28 2014

Targeting Self-Renewal in High-Grade Brain Tumors Leads to Loss of Brain Tumor Stem Cells and Prolonged Survival
Lineage tracing demonstrates that single Tlx⁺ cells can self-renew and generate Tlx⁻ tumor cells in primary tumors, suggesting that they are brain tumor stem cells (BTSCs). After introducing a BTSC-specific knock-out of the Tlx gene in primary mouse tumors, researchers observed a loss of self-renewal of BTSCs and prolongation of animal survival, accompanied by induction of essential signaling pathways mediating cell-cycle arrest, cell death, and neural differentiation. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release

ALK5-Dependent TGF-β Signaling Is a Major Determinant of Late-Stage Adult Neurogenesis
Consistent with a function of transforming growth factor-β (TGF-β) signaling in adult neurogenesis, genetic deletion of the TGF-β receptor ALK5 reduced the number, migration and dendritic arborization of newborn neurons. Conversely, constitutive activation of neuronal ALK5 in forebrain caused a marked increase in these aspects of neurogenesis and was associated with higher expression of c-Fos in newborn neurons and with stronger memory function. [Nat Neurosci] Abstract

Lineage-Specific Splicing of a Brain-Enriched Alternative Exon Promotes Glioblastoma Progression
Investigators determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. [J Clin Invest] Full Article | Press Release

Brain Pericytes Acquire a Microglial Phenotype after Stroke
Scientists investigated the role of pericytes in ischemic stroke. They demonstrated that human brain-derived pericytes adopt a microglial phenotype and upregulate mRNA specific for activated microglial cells under hypoxic conditions in vitro. [Acta Neuropathol] Full Article | Press Release

A TIGAR-Regulated Metabolic Pathway Is Critical for Protection of Brain Ischemia
The authors hypothesized that TP53-induced glycolysis and apoptosis regulator (TIGAR) plays a neuroprotective role in brain ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative stress. They found that TIGAR was highly expressed in brain neurons and was rapidly upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. [J Neurosci] Abstract

Cdk5-Dependent Mst3 Phosphorylation and Activity Regulate Neuronal Migration through RhoA Inhibition
Scientists showed that Mst3, a serine/threonine kinase highly expressed in the developing mouse brain, is essential for radial neuronal migration and final neuronal positioning in the developing mouse neocortex. [J Neurosci] Abstract

Selective Activation of mTORC1 Signaling Recapitulates Microcephaly, Tuberous Sclerosis, and Neurodegenerative Diseases
Researchers generated transgenic mice expressing a gain-of-function mutant of mammalian target of rapamycin (mTOR) in the forebrain in a temporally controlled manner. Selective activation of mTORC1 in embryonic stages induced cortical atrophy caused by prominent apoptosis of neuronal progenitors, associated with upregulation of HIF-1α. [Cell Rep] Abstract | Full Article | Graphical Abstract

Neurotrope, Inc. Collaborating with Dr. Paul Wender and Stanford University on Bryostatin Analogues
Neurotrope, Inc. announced that it has signed an agreement with Stanford University to study and, along with Dr. Paul Wender, investigate certain analogs of bryostatin, referred to as “bryologs”, as potential clinical candidates for the treatment of various neurological disorders. [Neurotrope, Inc.] Press Release

Maryland Stem Cell Research Commission Funds 31 New Research Proposals in FY 2014 with Continued Focus on Contributing to Cures for Debilitating Diseases and Conditions
The board of directors of the Maryland Technology Development Corporation approved the Commission’s recommendation to fund 31 new proposals with the Maryland Stem Cell Research Fund’s $10.4 million FY2014 budget. [Maryland Stem Cell Research Fund] Press Release

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