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https://www.readbyqxmd.com/read/28975414/high-level-of-ctp-synthase-induces-formation-of-cytoophidia-in-cortical-neurons-and-impairs-corticogenesis
#1
Xuzhao Li, Jiongfang Xie, Maofang Hei, Jianli Tang, Yanqing Wang, Eckart Förster, Shanting Zhao
De novo synthesis of the nucleotide CTP is catalyzed by the essential pyrimidine biosynthesis enzyme CTP synthase (CTPs), which forms large-scale filamentous structures consisting of CTPs termed cytoophidia in prokaryotes and in eukaryotes. Recent studies have shown that cytoophidia are abundant in neuroepithelial stem cells in Drosophila optic lobes and that overexpression of CTPs impairs optic lobe development. Whether CTPs and cytoophidia also play a role in the development of the mammalian cortex remains elusive...
October 3, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28939666/the-e2a-splice-variant-e47-regulates-the-differentiation-of-projection-neurons-via-p57-kip2-during-cortical-development
#2
Sabrina Pfurr, Yu-Hsuan Chu, Christian Bohrer, Franziska Greulich, Robert Beattie, Könül Mammadzada, Miriam Hils, Sebastian J Arnold, Verdon Taylor, Kristina Schachtrup, N Henriette Uhlenhaut, Christian Schachtrup
During corticogenesis, distinct classes of neurons are born from progenitor cells located in the ventricular and subventricular zones, from where they migrate towards the pial surface to assemble into highly organized layer-specific circuits. However, the precise and coordinated transcriptional network activity defining neuronal identity is still not understood. Here, we show that genetic depletion of the basic helix-loop-helix (bHLH) transcription factor E2A splice variant E47 increased the number of Tbr1-positive deep layer and Satb2-positive upper layer neurons at E14...
September 22, 2017: Development
https://www.readbyqxmd.com/read/28933765/potential-role-of-microtubule-stabilizing-agents-in-neurodevelopmental-disorders
#3
REVIEW
Sara Anna Bonini, Andrea Mastinu, Giulia Ferrari-Toninelli, Maurizio Memo
Neurodevelopmental disorders (NDDs) are characterized by neuroanatomical abnormalities indicative of corticogenesis disturbances. At the basis of NDDs cortical abnormalities, the principal developmental processes involved are cellular proliferation, migration and differentiation. NDDs are also considered "synaptic disorders" since accumulating evidence suggests that NDDs are developmental brain misconnection syndromes characterized by altered connectivity in local circuits and between brain regions. Microtubules and microtubule-associated proteins play a fundamental role in the regulation of basic neurodevelopmental processes, such as neuronal polarization and migration, neuronal branching and synaptogenesis...
July 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28899007/the-spectrum-of-structural-and-functional-network-alterations-in-malformations-of-cortical-development
#4
Seok-Jun Hong, Boris C Bernhardt, Ravnoor S Gill, Neda Bernasconi, Andrea Bernasconi
Neuroimaging studies of malformations of cortical development have mainly focused on the characterization of the primary lesional substrate, while whole-brain investigations remain scarce. Our purpose was to assess large-scale brain organization in prevalent cortical malformations. Based on experimental evidence suggesting that distributed effects of focal insults are modulated by stages of brain development, we postulated differential patterns of network anomalies across subtypes of malformations. We studied a cohort of patients with focal cortical dysplasia type II (n = 63), subcortical nodular heterotopia (n = 44), and polymicrogyria (n = 34), and compared them to 82 age- and sex-matched controls...
August 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28837264/rna-on-the-brain-emerging-layers-of-post-transcriptional-regulation-in-cerebral-cortex-development
#5
REVIEW
Ashley L Lennox, Hanqian Mao, Debra L Silver
Embryonic development is a critical period during which neurons of the brain are generated and organized. In the developing cerebral cortex, this requires complex processes of neural progenitor proliferation, neuronal differentiation, and migration. Each step relies upon highly regulated control of gene expression. In particular, RNA splicing, stability, localization, and translation have emerged as key post-transcriptional regulatory nodes of mouse corticogenesis. Trans-regulators of RNA metabolism, including microRNAs (miRs) and RNA-binding proteins (RBPs), orchestrate diverse steps of cortical development...
August 24, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28816361/msel-1l-deficiency-affects-vasculogenesis-and-neural-stem-cell-lineage-commitment
#6
Marina Cardano, Giuseppe R Diaferia, Luciano Conti, Simona Baronchelli, Alessandro Sessa, Vania Broccoli, Andrea Barbieri, Pasquale De Blasio, Ida Biunno
mSEL-1L is a highly conserved ER-resident type I protein, involved in the degradation of misfolded peptides through the ubiquitin-proteasome system (UPS), a pathway known to control the plasticity of the vascular smooth muscle cells (VSMC) phenotype and survival. In this article, we demonstrate that mSEL-1L deficiency interferes with the murine embryonic vascular network, showing particular irregularities in the intracranic and intersomitic neurovascular units and in the cerebral capillary microcirculation...
August 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28803787/expression-analyses-of-phactr1-phosphatase-and-actin-regulator-1-during-mouse-brain-development
#7
Hidenori Ito, Makoto Mizuno, Kei Noguchi, Rika Morishita, Ikuko Iwamoto, Akira Hara, Koh-Ichi Nagata
Phactr1 (Phosphatase and actin regulator 1) is abundantly expressed in the central nervous system and considered to regulate various neuronal processes through the regulation of protein phosphorylation and actin cytoskeletal organization. In this study, we prepared a specific antibody against Phactr1, anti-Phactr1, and carried out biochemical and morphological analyses of Phactr1 with mouse brain tissues. Western blotting analyses revealed that Phactr1 was expressed in a tissue-dependent profile in the young adult mouse and in a developmental stage-dependent manner in the mouse brain...
August 10, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28790015/retinoic-acid-controls-early-neurogenesis-in-the-developing-mouse-cerebral-cortex
#8
Carole Haushalter, Laure Asselin, Valérie Fraulob, Pascal Dollé, Muriel Rhinn
A tight regulation of neuron production is required to generate a functional cerebral cortex and is achieved by a proper balance between proliferation and differentiation of progenitor cells. Though the vitamin A (retinol) active derivative retinoic acid (RA) has been implicated as one of the signals acting during mammalian forebrain neurogenesis, its function at the onset of neurogenesis as well as during establishment of cortical layers and neuronal subtypes remains elusive. One limitation is that murine mutants for genes encoding key enzymes involved in RA synthesis die during early embryonic development...
October 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28781964/loss-of-suppressor-of-fused-in-mid-corticogenesis-leads-to-the-expansion-of-intermediate-progenitors
#9
Odessa R Yabut, Hui Xuan Ng, Gloria Fernandez, Keejung Yoon, Jeremy Kuhn, Samuel J Pleasure
Neural progenitors in the embryonic neocortex must be tightly regulated in order to generate the correct number and projection neuron subtypes necessary for the formation of functional neocortical circuits. In this study, we show that the intracellular protein Suppressor of Fused (Sufu) regulates the proliferation of intermediate progenitor (IP) cells at later stages of corticogenesis to affect the number of Cux1+ upper layer neurons in the postnatal neocortex. This correlates with abnormal levels of the repressor form of Gli3 (Gli3R) and the ectopic expression of Patched 1 (Ptch1), a Sonic Hedgehog (Shh) target gene...
December 2016: Journal of Developmental Biology
https://www.readbyqxmd.com/read/28757360/fusion-of-regionally-specified-hpsc-derived-organoids-models-human-brain-development-and-interneuron-migration
#10
Yangfei Xiang, Yoshiaki Tanaka, Benjamin Patterson, Young-Jin Kang, Gubbi Govindaiah, Naomi Roselaar, Bilal Cakir, Kun-Yong Kim, Adam P Lombroso, Sung-Min Hwang, Mei Zhong, Edouard G Stanley, Andrew G Elefanty, Janice R Naegele, Sang-Hun Lee, Sherman M Weissman, In-Hyun Park
Organoid techniques provide unique platforms to model brain development and neurological disorders. Whereas several methods for recapitulating corticogenesis have been described, a system modeling human medial ganglionic eminence (MGE) development, a critical ventral brain domain producing cortical interneurons and related lineages, has been lacking until recently. Here, we describe the generation of MGE and cortex-specific organoids from human pluripotent stem cells that recapitulate the development of MGE and cortex domains, respectively...
July 26, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28753911/morphological-and-molecular-basis-of-cytoplasmic-dilation-and-swelling-in-cortical-migrating-neurons
#11
REVIEW
Yoshiaki V Nishimura, Yo-Ichi Nabeshima, Takeshi Kawauchi
During corticogenesis, neuronal migration is an essential step for formation of a functional brain, and abnormal migration is known to cause various neurological disorders. Neuronal migration is not just a simple movement of the cell body, but a consequence of various morphological changes and coordinated subcellular events. Recent advances in in vivo and ex vivo cell biological approaches, such as in utero gene transfer, slice culture and ex vivo chemical inhibitor techniques, have revealed details of the morphological and molecular aspects of neuronal migration...
July 19, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28701923/cell-polarity-in-cerebral-cortex-development-cellular-architecture-shaped-by-biochemical-networks
#12
REVIEW
Andi H Hansen, Christian Duellberg, Christine Mieck, Martin Loose, Simon Hippenmeyer
The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28690640/wdr62-regulates-early-neural-and-glial-progenitor-specification-of-human-pluripotent-stem-cells
#13
Abdullah J Alshawaf, Ana Antonic, Efstratios Skafidas, Dominic Chi-Hung Ng, Mirella Dottori
Mutations in WD40-repeat protein 62 (WDR62) are commonly associated with primary microcephaly and other developmental cortical malformations. We used human pluripotent stem cells (hPSC) to examine WDR62 function during human neural differentiation and model early stages of human corticogenesis. Neurospheres lacking WDR62 expression showed decreased expression of intermediate progenitor marker, TBR2, and also glial marker, S100β. In contrast, inhibition of c-Jun N-terminal kinase (JNK) signalling during hPSC neural differentiation induced upregulation of WDR62 with a corresponding increase in neural and glial progenitor markers, PAX6 and EAAT1, respectively...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28687747/lamin-b1-levels-modulate-differentiation-into-neurons-during-embryonic-corticogenesis
#14
Sameehan Mahajani, Caterina Giacomini, Federica Marinaro, Davide De Pietri Tonelli, Andrea Contestabile, Laura Gasparini
Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknown. Here, we report that Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs) into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion favors NSC differentiation into glial fibrillar acidic protein (GFAP)-immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1) increases the proportion of neurons...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28647514/aqueous-cigarette-tar-extracts-disrupt-corticogenesis-from-human-embryonic-stem-cells-in-vitro
#15
Aynun N Begum, Jose S Aguilar, Yiling Hong
BACKGROUND: Cigarette butts are the most common form of litter in the world, and approximately 4.5 trillion smoked cigarettes are discarded every year worldwide. Cigarette butts contain over 4000 chemicals, many of which are known to have neurotoxic effects. Stem cell neuronal differentiation provides an excellent cellular model with which to examine the impact of aqueous cigarette tar extracts (ACTEs) on neurodevelopment. METHODS: We have developed a neurosphere-based stem cell neuronal differentiation protocol that can recapitulate corticogenesis and produce cell types that are similar to upper and lower layer cortical projection neurons found in the germinal zone of the developing human cortex...
October 2017: Environmental Research
https://www.readbyqxmd.com/read/28595951/sumoylation-regulates-the-transcriptional-activity-of-different-human-nfat-isoforms-in-neurons
#16
Hanna Vihma, Tõnis Timmusk
In the nervous system, four calcium/calcineurin-regulated members of the nuclear factor of activated T-cells (NFAT) family of transcription factors, NFATc1-c4, are involved in many developmental and functional processes, such as corticogenesis, synaptogenesis, synaptic plasticity and neurotransmission, that all need precise gene regulation. Therefore it is important to understand molecular events that contribute to the regulation of the transcriptional activity of specific NFAT isoforms. Previously, we have shown that there are a number of alternative splice variants of NFAT genes expressed in the brain and that neuronal activity leads to isoform-specific transactivation capacities of different human NFAT proteins...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28583079/lateral-cortical-cdca7-expression-levels-are-regulated-by-pax6-and-influence-the-production-of-intermediate-progenitors
#17
Yu-Ting Huang, John O Mason, David J Price
BACKGROUND: We studied whether regulation of Cdca7 (Cell division cycle associated 7) expression by transcription factor Pax6 contributes to Pax6's cellular actions during corticogenesis. The function of Cdca7 in mediating Pax6's effects during corticogenesis has not been explored. Pax6 is expressed by radial glial progenitors in the ventricular zone of the embryonic cortical neuroepithelium, where it is required for the development of a normal complement of Tbr2-expressing intermediate progenitor cells in the subventricular zone...
June 5, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28506232/rp58-and-p27-kip1-coordinate-cell-cycle-exit-and-neuronal-migration-within-the-embryonic-mouse-cerebral-cortex
#18
Olivier Clément, Isabel Anne Hemming, Ivan Enghian Gladwyn-Ng, Zhengdong Qu, Shan Shan Li, Michael Piper, Julian Ik-Tsen Heng
BACKGROUND: During the development of the mammalian cerebral cortex, newborn postmitotic projection neurons are born from local neural stem cells and must undergo radial migration so as to position themselves appropriately to form functional neural circuits. The zinc finger transcriptional repressor Rp58 (also known as Znf238 or Zbtb18) is critical for coordinating corticogenesis, but its underlying molecular mechanism remains to be better characterised. FINDINGS: Here, we demonstrate that the co-expression of Rp58 and the cyclin dependent kinase inhibitor (CDKI) p27(kip1) is important for E14...
May 15, 2017: Neural Development
https://www.readbyqxmd.com/read/28493553/regulation-of-cytokinesis-during-corticogenesis-focus-on-the-midbody
#19
REVIEW
Caroline A Johnson, Catherine E Wright, H Troy Ghashghaei
Development of the cerebral cortices depends on tight regulation of cell divisions. In this system, stem and progenitor cells undergo symmetric and asymmetric divisions to ultimately produce neurons that establish the layers of the cortex. Cell division culminates with the formation of the midbody, a transient organelle that establishes the site of abscission between nascent daughter cells. During cytokinetic abscission, the final stage of cell division, one daughter cell will inherit the midbody remnant, which can then maintain or expel the remnant, but mechanisms and circumstances influencing this decision are unclear...
May 11, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28467410/smek-promotes-corticogenesis-through-regulating-mbd3-s-stability-and-mbd3-nurd-complex-recruitment-to-genes-associated-with-neurogenesis
#20
Byoung-San Moon, Hyung-Mun Yun, Wen-Hsuan Chang, Bradford H Steele, Mingyang Cai, Si Ho Choi, Wange Lu
The fate of neural progenitor cells (NPCs) during corticogenesis is determined by a complex interplay of genetic or epigenetic components, but the underlying mechanism is incompletely understood. Here, we demonstrate that Suppressor of Mek null (Smek) interact with methyl-CpG-binding domain 3 (Mbd3) and the complex plays a critical role in self-renewal and neuronal differentiation of NPCs. We found that Smek promotes Mbd3 polyubiquitylation and degradation, blocking recruitment of the repressive Mbd3/nucleosome remodeling and deacetylase (NuRD) complex at the neurogenesis-associated gene loci, and, as a consequence, increasing acetyl histone H3 activity and cortical neurogenesis...
May 2017: PLoS Biology
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