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Kolsoum InanlooRahatloo, Fatemeh Peymani, Kimia Kahrizi, Hossein Najmabadi
A significant level of genetic heterogeneity has been demonstrated in intellectual disability (ID). More than 700 genes have been identified in ID patients. To identify molecular pathways underlying this heterogeneity, we applied whole transcriptome analysis using RNA-Seq in consanguineous families with ID. Significant changes in expression of genes related to neuronal and actin cytoskeletal functions were observed in all the ID families. Remarkably, we found a significant downregulation of SHTN1 gene and upregulation of FGFR2 gene in all ID patients...
February 8, 2019: Neuroscience
Min Zhang, Volkan Ergin, Lin Lin, Cheryl Stork, Liang Chen, Sika Zheng
How a neuron acquires an axon is a fundamental question. Piecemeal identification of many axonogenesis-related genes has been done, but coordinated regulation is unknown. Through unbiased transcriptome profiling of immature primary cortical neurons during early axon formation, we discovered an association between axonogenesis and neuron-specific alternative splicing. Known axonogenesis genes exhibit little expression alternation but widespread splicing changes. Axonogenesis-associated splicing is governed by RNA binding protein PTBP2, which is enriched in neurons and peaks around axonogenesis in the brain...
January 30, 2019: Neuron
Mariano Bisbal, Mónica Sanchez
Neurons are the most extensive and polarized cells that display a unique single long axon and multiple dendrites, which are compartments exhibiting structural and functional differences. Polarity occurs early in neuronal development and it is maintained by complex subcellular mechanisms throughout cell life. A well-defined and controlled spatio-temporal program of cellular and molecular events strictly regulates the formation of the axon and dendrites from a non-polarized cell. This event is critical for an adequate neuronal wiring and therefore for the normal functioning of the nervous system...
May 2019: Neural Regeneration Research
Cheng Huang, Xun Yang, Benhua Zeng, Li Zeng, Xue Gong, Chanjuan Zhou, Jinjun Xia, Bin Lian, Yinhua Qin, Lining Yang, Lanxiang Liu, Peng Xie
Major depressive disorders impact approximately 17% of the population worldwide, whose high morbidity and considerable adversity have resulted in enormous social and economic burden. In addition, clinically depressed patients often show reduced volume of olfactory bulb (OB) and decreased olfactory sensitivity. Although mounting evidence conveyed that the gut microbiota may implicate the pathophysiology of major depressive disorder (MDD) via the microbe-gut-brain axis, knowledge about its distinctive molecular mechanism is rudimentary...
December 4, 2018: Journal of Proteomics
Majd M Ariss, Abul B M M K Islam, Meg Critcher, Maria Paula Zappia, Maxim V Frolov
The function of Retinoblastoma tumor suppressor (pRB) is greatly influenced by the cellular context, therefore the consequences of pRB inactivation are cell-type-specific. Here we employ single cell RNA-sequencing (scRNA-seq) to profile the impact of an Rbf mutation during Drosophila eye development. First, we build a catalogue of 11,500 wild type eye disc cells containing major known cell types. We find a transcriptional switch occurring in differentiating photoreceptors at the time of axonogenesis. Next, we map a cell landscape of Rbf mutant and identify a mutant-specific cell population that shows intracellular acidification due to increase in glycolytic activity...
November 27, 2018: Nature Communications
Albert Kelly, Aisling O'Malley, Mohammad Redha, Gerard W O'Keeffe, Denis S Barry
Glycosylation is a major post-translational modification in which a carbohydrate known as a glycan is enzymatically attached to target proteins which regulate protein folding and stability. Glycans are strongly expressed in the developing nervous system where they play multiple roles during development. The importance of these glycan epitopes in neural development is highlighted by a group of conditions known as congenital disorders of glycosylation which lead to psychomotor difficulties, mental retardation, lissencephaly, microencephaly and epilepsy...
November 25, 2018: Journal of Anatomy
Yona Goldshmit, Jean Kitty K Y Tang, Ashley L Siegel, Phong D Nguyen, Jan Kaslin, Peter D Currie, Patricia R Jusuf
BACKGROUND: Despite conserved developmental processes and organization of the vertebrate central nervous system, only some vertebrates including zebrafish can efficiently regenerate neural damage including after spinal cord injury. The mammalian spinal cord shows very limited regeneration and neurogenesis, resulting in permanent life-long functional impairment. Therefore, there is an urgent need to identify the cellular and molecular mechanisms that can drive efficient vertebrate neurogenesis following injury...
November 17, 2018: Neural Development
Marianna Madeo, Paul L Colbert, Daniel W Vermeer, Christopher T Lucido, Jacob T Cain, Elisabeth G Vichaya, Aaron J Grossberg, DesiRae Muirhead, Alex P Rickel, Zhongkui Hong, Jing Zhao, Jill M Weimer, William C Spanos, John H Lee, Robert Dantzer, Paola D Vermeer
Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and murine in vivo models to test this hypothesis. When appropriately stimulated, PC12 cells extend processes, called neurites. We show that patient tumors release vesicles, called exosomes, which induce PC12 neurite outgrowth...
October 16, 2018: Nature Communications
Chiara Mencarelli, Justyna Nitarska, Tim Kroecher, Francesco Ferraro, Katherine Massey, Antonella Riccio, Franck Pichaud
Neuronal polarity in the developing cortex begins during the early stages of neural progenitor migration toward the cortical plate and culminates with the specification of the axon and dendrites. Here, we demonstrate that the Ran-dependent nucleocytoplasmic transport machinery is essential for the establishment of cortical neuron polarity. We found that Ran-binding protein 1 (RanBP1) regulates axon specification and dendritic arborization in cultured neurons in vitro and radial neural migration in vivo. During axonogenesis, RanBP1 regulates the cytoplasmic levels of the polarity protein LKB1/Par4, and this is dependent on the nuclear export machinery...
September 4, 2018: Cell Reports
Stefano Berto, Katja Nowick
The human prefrontal cortex (PFC) differs from that of other primates with respect to size, histology, and functional abilities. Here, we analyzed genome-wide expression data of humans, chimpanzees, and rhesus macaques to discover evolutionary changes in transcription factor (TF) networks that may underlie these phenotypic differences. We determined the co-expression networks of all TFs with species-specific expression including their potential target genes and interaction partners in the PFC of all three species...
August 1, 2018: Genome Biology and Evolution
Eriko Shimada, Fasih M Ahsan, Mahta Nili, Dian Huang, Sean Atamdede, Tara TeSlaa, Dana Case, Xiang Yu, Brian D Gregory, Benjamin J Perrin, Carla M Koehler, Michael A Teitell
Polynucleotide phosphorylase (PNPase) is an essential mitochondria-localized exoribonuclease implicated in multiple biological processes and human disorders. To reveal role(s) for PNPase in mitochondria, we established PNPase knockout (PKO) systems by first shifting culture conditions to enable cell growth with defective respiration. Interestingly, PKO established in mouse embryonic fibroblasts (MEFs) resulted in the loss of mitochondrial DNA (mtDNA). The transcriptional profile of PKO cells was similar to rho0 mtDNA deleted cells, with perturbations in cholesterol (FDR = 6...
2018: PloS One
Mariano Bisbal, Mónica Remedi, Gonzalo Quassollo, Alfredo Cáceres, Mónica Sanchez
Rotenone, a broad-spectrum insecticide, piscicide and pesticide, produces a complete and selective suppression of axonogenesis in cultured hippocampal neurons. This effect is associated with an inhibition of actin dynamics through activation of Ras homology member A (RhoA) activity. However, the upstream signaling mechanisms involved in rotenone-induced RhoA activation were unknown. We hypothesized that rotenone might inhibit axon growth by the activation of RhoA/ROCK pathway because of the changes in microtubule (MT) dynamics and the concomitant release of Lfc, a MT-associated Guanine Nucleotide Exchange Factor (GEF) for RhoA...
July 4, 2018: Journal of Neurochemistry
Amrutha Swaminathan, Rahma Hassan-Abdi, Solène Renault, Aleksandra Siekierska, Raphaëlle Riché, Meijiang Liao, Peter A M de Witte, Constantin Yanicostas, Nadia Soussi-Yanicostas, Pierre Drapeau, Éric Samarut
Mutations in DEPDC5 are causal factors for a broad spectrum of focal epilepsies, but the underlying pathogenic mechanisms are still largely unknown. To address this question, a zebrafish depdc5 knockout model showing spontaneous epileptiform events in the brain, increased drug-induced seizure susceptibility, general hypoactivity, premature death at 2-3 weeks post-fertilization, as well as the expected hyperactivation of mTOR signaling was developed. Using this model, the role of DEPDC5 in brain development was investigated using an unbiased whole-transcriptomic approach...
June 18, 2018: Current Biology: CB
Animesh Banerjee, Jagat Kumar Roy
During development, axonogenesis, an integral part of neurogenesis, is based on well-concerted events comprising generation, rearrangement, migration, elongation, and adhesion of neurons. Actin, specifically the crosstalk between the guardians of actin polymerization, like enabled, chickadee, capping protein plays an essential role in crafting several events of axonogenesis. Recent evidences reflect multifaceted role of microRNA during axonogenesis. Here, we investigated the role of bantam miRNA, a well-established miRNA in Drosophila, in regulating the actin organization during brain development...
May 18, 2018: Invertebrate Neuroscience: IN
Robert W Ledeen, Jürgen Kopitz, José Abad-Rodríguez, Hans-Joachim Gabius
Molecular signals on the cell surface are responsible for adhesion and communication. Of relevance in this respect, their chemical properties endow carbohydrates with the capacity to store a maximum of information in a minimum of space. One way to present glycans on the cell surface is their covalent conjugation to a ceramide anchor. Among the resulting glycosphingolipids, gangliosides are special due to the presence of at least one sialic acid in the glycan chains. Their spatial accessibility and the dynamic regulation of their profile are factors that argue in favor of a role of glycans of gangliosides as ligands (counterreceptors) for carbohydrate-binding proteins (lectins)...
2018: Progress in Molecular Biology and Translational Science
Li-Ning Su, Xiao-Qing Song, Zhan-Xia Xue, Chen-Qing Zheng, Hai-Feng Yin, Hui-Ping Wei
Axon regeneration is crucial for recovery from neurological diseases. Numerous studies have identified several genes, microRNAs (miRNAs), and transcription factors (TFs) that influence axon regeneration. However, the regulatory networks involved have not been fully elucidated. In the present study, we analyzed a regulatory network of 51 miRNAs, 27 TFs, and 59 target genes, which is involved in axon regeneration. We identified 359 pairs of feed-forward loops (FFLs), seven important genes (Nap1l1, Arhgef12, Sema6d, Akt3, Trim2, Rab11fip2, and Rps6ka3), six important miRNAs (hsa-miR-204-5p, hsa-miR-124-3p, hsa-miR-26a-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-15b-5p), and eight important TFs (Smada2, Fli1, Wt1, Sp6, Sp3, Smad4, Smad5, and Creb1), which appear to play an important role in axon regeneration...
2018: Journal of Zhejiang University. Science. B
Yin Yuan, Xiu-Yue Xu, Jie Lao, Xin Zhao
Nerve transfer is the most common treatment for total brachial plexus avulsion injury. After nerve transfer, the movement of the injured limb may be activated by certain movements of the healthy limb at the early stage of recovery, i.e., trans-hemispheric reorganization. Previous studies have focused on functional magnetic resonance imaging and changes in brain-derived neurotrophic factor and growth associated protein 43, but there have been no proteomics studies. In this study, we designed a rat model of total brachial plexus avulsion injury involving contralateral C7 nerve transfer...
February 2018: Neural Regeneration Research
Tu-Hsueh Yeh, Han-Fang Liu, Yu-Wen Li, Chin-Song Lu, Hung-Yu Shih, Ching-Chi Chiu, Sheng-Jia Lin, Yin-Cheng Huang, Yi-Chuan Cheng
Hexanucleotide repeat expansions in the C9orf72 gene are a common genetic cause of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the function of C9orf72 in neural development and the pathogenic mechanism underlying neurodegeneration are unknown. We found that disrupting C9orf72 expression by using C9orf72 constructs that lack the complete DENN domain result in reduced GTPase activity in zebrafish embryos, demonstrating the indispensability of the complete DENN domain...
June 2018: Experimental Neurology
Amanda K Tilot, Katerina S Kucera, Arianna Vino, Julian E Asher, Simon Baron-Cohen, Simon E Fisher
Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural and functional neural connectivity, but the underlying molecular mechanisms are unknown. The trait also appears to be more common among people with autism spectrum disorder and savant abilities. Previous linkage studies searching for shared loci of large effect size across multiple families have had limited success...
March 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jin Kim, Hanseul Oh, Bokyeong Ryu, Ukjin Kim, Ji Min Lee, Cho-Rok Jung, C-Yoon Kim, Jae-Hak Park
Triclosan (TCS) is an organic compound with a wide range of antibiotic activity and has been widely used in items ranging from hygiene products to cosmetics; however, recent studies suggest that it has several adverse effects. In particular, TCS can be passed to both fetus and infants, and while some evidence suggests in vitro neurotoxicity, there are currently few studies concerning the mechanisms of TCS-induced developmental neurotoxicity. Therefore, this study aimed to clarify the effect of TCS on neural development using zebrafish models, by analyzing the morphological changes, the alterations observed in fluorescence using HuC-GFP and Olig2-dsRED transgenic zebrafish models, and neurodevelopmental gene expression...
May 2018: Environmental Pollution
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