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Jan Kriska, Pavel Honsa, David Dzamba, Olena Butenko, Denisa Kolenicova, Lucie Janeckova, Zuzana Nahacka, Ladislav Andera, Zbynek Kozmik, M Mark Taketo, Vladimir Korinek, Miroslava Anderova
The canonical Wnt signaling pathway plays an important role in embryogenesis, and the establishment of neurogenic niches. It is involved in proliferation and differentiation of neural progenitors, since elevated Wnt/β-catenin signaling promotes differentiation of neural stem/progenitor cells (NS/PCs(1)) towards neuroblasts. Nevertheless, it remains elusive how the differentiation program of neural progenitors is influenced by the Wnt signaling output. Using transgenic mouse models, we found that in vitro activation of Wnt signaling resulted in higher expression of β-catenin protein and Wnt/β-catenin target genes, while Wnt signaling inhibition resulted in the reverse effect...
September 19, 2016: Brain Research
Youqiong Ye, Liang Gu, Xiaolong Chen, Jiejun Shi, Xiaobai Zhang, Cizhong Jiang
Chromatin remodeling plays a critical role in gene regulation and impacts many biological processes. However, little is known about the relationship between chromatin remodeling dynamics and in vivo cell lineage commitment. Here, we reveal the patterns of histone modification change and nucleosome positioning dynamics and their epigenetic regulatory roles during the in vivo glial differentiation in early Drosophila embryos. The genome-wide average H3K9ac signals in promoter regions are decreased in the glial cells compared to the neural progenitor cells...
2016: Scientific Reports
Eduardo E Arteaga-Bracho, Maria Gulinello, Michael L Winchester, Nandini Pichamoorthy, Jenna R Petronglo, Alicia D Zambrano, Julio Inocencio, Chirstopher D De Jesus, Joseph O Louie, Solen Gokhan, Mark F Mehler, Aldrin E Molero
The mutation in huntingtin (mHtt) leads to a spectrum of impairments in the developing forebrain of Huntington's disease (HD) mouse models. Whether these developmental alterations are due to loss- or gain-of-function mechanisms and contribute to HD pathogenesis is unknown. We examined the role of selective loss of huntingtin (Htt) function during development on postnatal vulnerability to cell death. We employed mice expressing very low levels of Htt throughout embryonic life to postnatal day 21 (Hdh(d•hyp))...
September 10, 2016: Neurobiology of Disease
Jimmy de Melo, Brian S Clark, Seth Blackshaw
Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs...
2016: Scientific Reports
J Alberto Ortega, Carissa L Sirois, Fani Memi, Nicole Glidden, Nada Zecevic
The oxygen (O2) concentration is a vital parameter for controlling the survival, proliferation, and differentiation of neural stem cells. A prenatal reduction of O2 levels (hypoxia) often leads to cognitive and behavioral defects, attributable to altered neural development. In this study, we analyzed the effects of O2 levels on human cortical progenitors, the radial glia cells (RGCs), during active neurogenesis, corresponding to the second trimester of gestation. Small changes in O2 levels profoundly affected RGC survival, proliferation, and differentiation...
September 6, 2016: Cerebral Cortex
Jingjun Li, Jing Ma, Guofeng Meng, Hong Lin, Sharon Wu, Jamie Wang, Jie Luo, Xiaohong Xu, David Tough, Matthew Lindon, Inma Rioja Pastor, Jing Zhao, Hongkang Mei, Rab Prinjha, Zhong Zhong
Neural stem cells and progenitor cells (NPCs) are increasingly appreciated to hold great promise for regenerative medicine to treat CNS injuries and neurodegenerative diseases. However, evidence for effective stimulation of neuronal production from endogenous or transplanted NPCs for neuron replacement with small molecules remains limited. To identify novel chemical entities/targets for neurogenesis, we had established a NPC phenotypic screen assay and validated it using known small-molecule neurogenesis inducers...
July 20, 2016: Stem Cell Research
Karl-F Bergeron, Chloé M A Nguyen, Tatiana Cardinal, Baptiste Charrier, David W Silversides, Nicolas Pilon
Waardenburg syndrome is a neurocristopathy characterized by a combination of skin/hair depigmentation and inner ear defects. In the type 4 form, these defects are comorbid with Hirschsprung disease, a disorder marked by an absence of neural ganglia in the distal colon triggering functional intestinal obstruction. Here, we report that the Spot mouse line - obtained through an insertional mutagenesis screen for genes involved in neural crest cell (NCC) development - is a model for Waardenburg syndrome type 4...
September 1, 2016: Disease Models & Mechanisms
Chiara Rolando, Andrea Erni, Alice Grison, Robert Beattie, Anna Engler, Paul J Gokhale, Marta Milo, Thomas Wegleiter, Sebastian Jessberger, Verdon Taylor
Adult neural stem cells (NSCs) are defined by their inherent capacity to self-renew and give rise to neurons, astrocytes, and oligodendrocytes. In vivo, however, hippocampal NSCs do not generate oligodendrocytes for reasons that have remained enigmatic. Here, we report that deletion of Drosha in adult dentate gyrus NSCs activates oligodendrogenesis and reduces neurogenesis at the expense of gliogenesis. We further find that Drosha directly targets NFIB to repress its expression independently of Dicer and microRNAs...
August 15, 2016: Cell Stem Cell
Jordan L Wright, Charlotte M Ermine, Jesper R Jørgensen, Clare L Parish, Lachlan H Thompson
A number of studies have shown that damage to brain structures adjacent to neurogenic regions can result in migration of new neurons from neurogenic zones into the damaged tissue. The number of differentiated neurons that survive is low, however, and this has led to the idea that the introduction of extrinsic signaling factors, particularly neurotrophic proteins, may augment the neurogenic response to a level that would be therapeutically relevant. Here we report on the impact of the relatively newly described neurotrophic factor, Meteorin, when over-expressed in the striatum following excitotoxic injury...
2016: Frontiers in Cellular Neuroscience
Yotam Menuchin-Lasowski, Pazit Oren-Giladi, Qing Xie, Raaya Ezra-Elia, Ron Ofri, Shany Peled-Hajaj, Chen Farhy, Yujiro Higashi, Tom Van de Putte, Hisato Kondoh, Danny Huylebroeck, Ales Cvekl, Ruth Ashery-Padan
The transcription factor Sip1 (Zeb2) plays multiple roles during CNS development from early acquisition of neural fate to cortical neurogenesis and gliogenesis. In humans, SIP1 (ZEB2) haploinsufficiency leads to Mowat-Wilson syndrome, a complex congenital anomaly including intellectual disability, epilepsy and Hirschsprung disease. Here we uncover the role of Sip1 in retinogenesis. Somatic deletion of Sip1 from mouse retinal progenitors primarily affects the generation of inner nuclear layer cell types, resulting in complete loss of horizontal cells and reduced numbers of amacrine and bipolar cells, while the number of Muller glia is increased...
August 1, 2016: Development
Carla Garza-Lombó, María E Gonsebatt
The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms...
2016: Frontiers in Cellular Neuroscience
Zoltán Rusznák, Willem Henskens, Emma Schofield, Woojin S Kim, YuHong Fu
The subgranular zone (SGZ) and subventricular zone (SVZ) are developmental remnants of the germinal regions of the brain, hence they retain the ability to generate neuronal progenitor cells in adult life. Neurogenesis in adult brain has an adaptive function because newly produced neurons can integrate into and modify existing neuronal circuits. In contrast to the SGZ and SVZ, other brain regions have a lower capacity to produce new neurons, and this usually occurs via parenchymal and periventricular cell genesis...
June 2016: Experimental Neurobiology
Xiao Huang, Yan-Li Luo, Yue-Shi Mao, Jian-Lin Ji
The major depressive disorder (MDD) is a relatively common mental disorder from which that hundreds of million people have suffered, leading to displeasing life quality, which is characterized by health damage and even suicidal thoughts. The complicated development and functioning of MDD is still under exploration. Long noncoding RNA (lncRNAs) are highly expressed in the brain, could affect neural stem cell maintenance, neurogenesis and gliogenesis, brain patterning, synaptic and stress responses, and neural plasticity...
June 15, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Monica Benito-Muñoz, Carlos Matute, Fabio Cavaliere
We previously demonstrated that activation of ATP P2X receptors during oxygen and glucose deprivation inhibits neuroblast migration and in vitro neurogenesis from the subventricular zone (SVZ). Here, we have studied the effects of adenosine, the natural end-product of ATP hydrolysis, in modulating neurogenesis and gliogenesis from the SVZ. We provide immunochemical, molecular and pharmacological evidence that adenosine via A1 receptors reduces neuronal differentiation of neurosphere cultures generated from postnatal SVZ...
September 2016: Glia
Jonas Frisén
The brain constantly changes to store memories and adapt to new conditions. One type of plasticity that has gained increasing interest during the last years is the generation of new cells. The generation of both new neurons and glial cells contributes to neural plasticity and to some neural repair. There are substantial differences between mammalian species with regard to the extent of and mechanisms behind cell exchange in neural plasticity. Both neurogenesis and gliogenesis have several specific features in humans, which may contribute to the unique plasticity of the human brain...
June 1, 2016: Annual Review of Cell and Developmental Biology
Stephanie Njau, Shantanu H Joshi, Amber M Leaver, Megha Vasavada, Jessica Van Fleet, Randall Espinoza, Katherine L Narr
Though electroconvulsive therapy (ECT) is an established treatment for severe depression, the neurobiological factors accounting for the clinical effects of ECT are largely unknown. Myo-inositol, a neurometabolite linked with glial activity, is reported as reduced in fronto-limbic regions in patients with depression. Whether changes in myo-inositol relate to the antidepressant effects of ECT is unknown. Using magnetic resonance spectroscopy ((1)H-MRS), we measured dorsomedial anterior cingulate cortex (dmACC) and left and right hippocampal myo-inositol in 50 ECT patients (mean age: 43...
September 2016: Journal of Psychiatric Research
Margaret A Mohr, Francisca L Garcia, Lydia L DonCarlos, Cheryl L Sisk
The anteroventral periventricular nucleus (AVPV) orchestrates the neuroendocrine-positive feedback response that triggers ovulation in female rodents. The AVPV is larger and more cell-dense in females than in males, and during puberty, only females develop the capacity to show a positive feedback response. We previously reported a potential new mechanism to explain this female-specific gain of function during puberty, namely a female-biased sex difference in the pubertal addition of new cells to the rat AVPV...
June 2016: Endocrinology
Fabio Cavaliere, Monica Benito-Muñoz, Carlos Matute
Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models...
2016: Stem Cells International
Benedikt Berninger, Sebastian Jessberger
Neural stem/progenitor cells (NSPCs) retain their ability to generate newborn neurons throughout life in the mammalian brain. Here, we describe how recently developed virus- and transgenesis-based techniques will help us (1) to understand the functional effects of neurogenesis in health and disease, (2) to design novel approaches to harness the potential for NSPC-associated endogenous repair, and (3) to induce the generation of neurons outside the main neurogenic niches in the adult brain.
2016: Cold Spring Harbor Perspectives in Biology
Fatima Memic, Viktoria Knoflach, Rebecca Sadler, Gunilla Tegerstedt, Erik Sundström, Francois Guillemot, Vassilis Pachnis, Ulrika Marklund
UNLABELLED: The enteric nervous system (ENS) is organized into neural circuits within the gastrointestinal wall where it controls the peristaltic movements, secretion, and blood flow. Although proper gut function relies on the complex neuronal composition of the ENS, little is known about the transcriptional networks that regulate the diversification into different classes of enteric neurons and glia during development. Here we redefine the role of Ascl1 (Mash1), one of the few regulatory transcription factors described during ENS development...
April 13, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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