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Axonal guidance

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https://www.readbyqxmd.com/read/28202041/the-microtubule-plus-end-tracking-protein-tacc3-promotes-persistent-axon-outgrowth-and-mediates-responses-to-axon-guidance-signals-during-development
#1
Burcu Erdogan, Garrett M Cammarata, Eric J Lee, Benjamin C Pratt, Andrew F Francl, Erin L Rutherford, Laura Anne Lowery
BACKGROUND: Formation of precise neuronal connections requires proper axon guidance. Microtubules (MTs) of the growth cone provide a critical driving force during navigation of the growing ends of axons. Pioneer MTs and their plus-end tracking proteins (+TIPs) are thought to play integrative roles during this navigation. TACC3 is a + TIP that we have previously implicated in regulating MT dynamics within axons. However, the role of TACC3 in axon guidance has not been previously explored...
February 15, 2017: Neural Development
https://www.readbyqxmd.com/read/28201982/transcriptome-profile-of-rat-genes-in-injured-spinal-cord-at-different-stages-by-rna-sequencing
#2
Ling-Ling Shi, Nan Zhang, Xiu-Mei Xie, Yue-Juan Chen, Rui Wang, Lin Shen, Jian-Sheng Zhou, Jian-Guo Hu, He-Zuo Lü
BACKGROUND: Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology. RESULTS: RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group)...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28199838/islet-coordinately-regulates-motor-axon-guidance-and-dendrite-targeting-through-the-frazzled-dcc-receptor
#3
Celine Santiago, Greg J Bashaw
Motor neuron axon targeting in the periphery is correlated with the positions of motor neuron inputs in the CNS, but how these processes are coordinated to form a myotopic map remains poorly understood. We show that the LIM homeodomain factor Islet (Isl) controls targeting of both axons and dendrites in Drosophila motor neurons through regulation of the Frazzled (Fra)/DCC receptor. Isl is required for fra expression in ventrally projecting motor neurons, and isl and fra mutants have similar axon guidance defects...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28197551/ephrina5-signaling-is-required-for-the-distinctive-targeting-of-raphe-serotonin-neurons-in-the-forebrain
#4
Teng Teng, Afsaneh Gaillard, Aude Muzerelle, Patricia Gaspar
Serotonin (5-HT) neurotransmission in the brain relies on a widespread axon terminal network originating from the hindbrain raphe nuclei. These projections are topographically organized such that the dorsal (DR), and median raphe (MnR) nuclei have different brain targets. However, the guidance molecules involved in this selective targeting in development are unknown. Here, we show the implication of ephrinA5 signaling in this process. We find that the EphA5 gene is selectively expressed in a subset of 5-HT neurons during embryonic and postnatal development...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28197545/active-nerve-regeneration-with-failed-target-reinnervation-drives-persistent-neuropathic-pain
#5
Wenrui Xie, Judith A Strong, Jun-Ming Zhang
Peripheral nerves can regenerate and, when injured, may cause neuropathic pain. We propose that the active regeneration process plays a pivotal role in the maintenance of neuropathic pain. In one commonly used rodent neuropathic pain model, pronounced pain behaviors follow ligation and cutting of the L5 spinal nerve. We found that the injured nerve regenerates into the sciatic nerve and functionally reinnervates target tissues: the regenerated nerve conducts electrical signals, mechanical responses, and tracers between the leg/hindpaw and axotomized sensory ganglion...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28196860/the-nclx-type-na-ca-2-exchanger-ncx-9-is-required-for-patterning-of-neural-circuits-in-caenorhabditis-elegans
#6
Vishal Sharma, Soumitra Roy, Israel Sekler, Damien M O'Halloran
NCLX is a Na(+)/Ca(2+) exchanger that uses energy stored in the transmembrane sodium gradient to facilitate the exchange of sodium ions for ionic calcium. Mammals have a single NCLX, which has been shown to function primarily at the mitochondrion and is an important regulator of neuronal physiology by contributing to neurotransmission and synaptic plasticity. The role of NCLX in developmental cell patterning, for example, in neural circuits, is largely unknown. Here we describe a novel role for the Caenorhabditis elegans NCLX-type protein, NCX-9, in neural circuit formation...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28193234/differential-timing-of-neurogenesis-underlies-dorsal-ventral-topographic-projection-of-olfactory-sensory-neurons
#7
Eerdunfu, Naoki Ihara, Bao Ligao, Yuji Ikegaya, Haruki Takeuchi
BACKGROUND: The mammalian primary olfactory system has a spatially-ordered projection in which olfactory sensory neurons (OSNs) located in the dorsomedial (DM) and ventrolateral (VL) region of the olfactory epithelium (OE) send their axons to the dorsal and ventral region of the olfactory bulb (OB), respectively. We previously found that OSN axonal projections occur sequentially, from the DM to the VL region of the OE. The differential timing of axonal projections is important for olfactory map formation because early-arriving OSN axons secrete guidance cues at the OB to help navigate late-arriving OSN axons...
February 13, 2017: Neural Development
https://www.readbyqxmd.com/read/28187187/widespread-signatures-of-positive-selection-in-common-risk-alleles-associated-to-autism-spectrum-disorder
#8
Renato Polimanti, Joel Gelernter
The human brain is the outcome of innumerable evolutionary processes; the systems genetics of psychiatric disorders could bear their signatures. On this basis, we analyzed five psychiatric disorders, attention deficit hyperactivity disorder, autism spectrum disorder (ASD), bipolar disorder, major depressive disorder, and schizophrenia (SCZ), using GWAS summary statistics from the Psychiatric Genomics Consortium. Machine learning-derived scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation)...
February 10, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28184278/possible-sexually-dimorphic-role-of-mirna-and-other-sncrna-in-asd-brain
#9
Cynthia M Schumann, Frank R Sharp, Bradley P Ander, Boryana Stamova
BACKGROUND: Autism spectrum disorder (ASD) is sexually dimorphic in brain structure, genetics, and behaviors. In studies of brain tissue, the age of the population is clearly a factor in interpreting study outcome, yet sex is rarely considered. To begin to address this issue, we extend our previously published microarray analyses to examine expression of small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), in ASD and in the control temporal cortex in males and females. Predicted miRNA targets were identified as well as the pathways they overpopulate...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28171762/ephs-and-ephrins
#10
Hannah Taylor, Jessica Campbell, Catherine D Nobes
Eph receptors comprise the largest family of receptor tyrosine kinases (RTKs), with fourteen receptors divided into two subfamilies - EphAs and EphBs. Yet, despite their multitude of functions in almost all tissues of the body, these receptors represent one of the most underappreciated RTK families. What makes Eph receptors unique is that their cognate ligands, the ephrins, are tethered to the cell surface, in contrast to other RTKs whose ligands are generally soluble. This phenomenon means that signalling through Eph receptors is largely dependent on cell-cell contact...
February 6, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28169834/development-of-biomimetic-micro-patterned-device-incorporated-with-neurotrophic-gradient-and-supportive-schwann-cells-for-the-applications-in-neural-tissue-engineering
#11
Chia-Wei Yeh, Li-Wen Wang, Hsi-Chin Wu, Yi-Kong Hsieh, Jane Wang, Ming-Hong Chen, Tzu-Wei Wang
In these years, the artificial nerve guidance conduit has been developed as an alternative way to repair peripheral nerve injury. Unlike autologous nerve graft, the artificial nerve guidance conduit without proper stimulating factors and guidance cues still cannot obtain satisfactory prognosis for clinical patients. In this study, a biodegradable polymer-based implantable device has been developed and characterized. By incorporating three stimulating factors: 1) micro-patterned surface that can directionally guide the axon as physical cue; 2) neurotrophic gradient membrane that can continually attract axon outgrowth from the proximal to distal stump as chemical cue; 3) Schwann cells that can support the growth of neurite and form myelin sheath around axon as biological cue, we expect that this construct can be used as a promising nerve guidance conduit for peripheral nerve regeneration...
February 7, 2017: Biofabrication
https://www.readbyqxmd.com/read/28169354/three-dimensional-aligned-nanofibers-hydrogel-scaffold-for-controlled-non-viral-drug-gene-delivery-to-direct-axon-regeneration-in-spinal-cord-injury-treatment
#12
Lan Huong Nguyen, Mingyong Gao, Junquan Lin, Wutian Wu, Jun Wang, Sing Yian Chew
Spinal cord injuries (SCI) often lead to persistent neurological dysfunction due to failure in axon regeneration. Unfortunately, currently established treatments, such as direct drug administration, do not effectively treat SCI due to rapid drug clearance from our bodies. Here, we introduce a three-dimensional aligned nanofibers-hydrogel scaffold as a bio-functionalized platform to provide sustained non-viral delivery of proteins and nucleic acid therapeutics (small non-coding RNAs), along with synergistic contact guidance for nerve injury treatment...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28163913/where-does-axon-guidance-lead-us
#13
REVIEW
Esther Stoeckli
During neural circuit formation, axons need to navigate to their target cells in a complex, constantly changing environment. Although we most likely have identified most axon guidance cues and their receptors, we still cannot explain the molecular background of pathfinding for any subpopulation of axons. We lack mechanistic insight into the regulation of interactions between guidance receptors and their ligands. Recent developments in the field of axon guidance suggest that the regulation of surface expression of guidance receptors comprises transcriptional, translational, and post-translational mechanisms, such as trafficking of vesicles with specific cargos, protein-protein interactions, and specific proteolysis of guidance receptors...
2017: F1000Research
https://www.readbyqxmd.com/read/28158215/in-silico-analyses-and-global-transcriptional-profiling-reveal-novel-putative-targets-for-pea3-transcription-factor-related-to-its-function-in-neurons
#14
Başak Kandemir, Ugur Dag, Burcu Bakir Gungor, İlknur Melis Durasi, Burcu Erdogan, Eray Sahin, Ugur Sezerman, Isil Aksan Kurnaz
Pea3 transcription factor belongs to the PEA3 subfamily within the ETS domain transcription factor superfamily, and has been largely studied in relation to its role in breast cancer metastasis. Nonetheless, Pea3 plays a role not only in breast tumor, but also in other tissues with branching morphogenesis, including kidneys, blood vasculature, bronchi and the developing nervous system. Identification of Pea3 target promoters in these systems are important for a thorough understanding of how Pea3 functions. Present study particularly focuses on the identification of novel neuronal targets of Pea3 in a combinatorial approach, through curation, computational analysis and microarray studies in a neuronal model system, SH-SY5Y neuroblastoma cells...
2017: PloS One
https://www.readbyqxmd.com/read/28150729/short-stop-mediates-axonal-compartmentalization-of-mucin-type-core-1-glycans
#15
Takaaki Kinoshita, Chikara Sato, Takashi J Fuwa, Shoko Nishihara
T antigen, mucin-type core 1 O-glycan, is highly expressed in the embryonic central nervous system (CNS) and co-localizes with a Drosophila CNS marker, BP102 antigen. BP102 antigen and Derailed, an axon guidance receptor, are localized specifically in the proximal axon segment of isolated primary cultured neurons, and their mobility is restricted at the intra-axonal boundary by a diffusion barrier. However, the preferred trafficking mechanism remains unknown. In this study, the major O-glycan T antigen was found to localize within the proximal compartments of primary cultured Drosophila neurons, whereas the N-glycan HRP antigen was not...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28147273/mir-182-regulates-slit2-mediated-axon-guidance-by-modulating-the-local-translation-of-a-specific-mrna
#16
Anaïs Bellon, Archana Iyer, Simone Bridi, Flora C Y Lee, Cesaré Ovando-Vázquez, Eloina Corradi, Sara Longhi, Michela Roccuzzo, Stephanie Strohbuecker, Sindhu Naik, Peter Sarkies, Eric Miska, Cei Abreu-Goodger, Christine E Holt, Marie-Laure Baudet
During brain wiring, cue-induced axon behaviors such as directional steering and branching are aided by localized mRNA translation. Different guidance cues elicit translation of subsets of mRNAs that differentially regulate the cytoskeleton, yet little is understood about how specific mRNAs are selected for translation. MicroRNAs (miRNAs) are critical translational regulators that act through a sequence-specific mechanism. Here, we investigate the local role of miRNAs in mRNA-specific translation during pathfinding of Xenopus laevis retinal ganglion cell (RGC) axons...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28135886/contactin-2-tag-1-active-on-the-front-line-for-three-decades
#17
Tomoyuki Masuda
Contactin-2/transiently expressed axonal surface glycoprotein-1 (TAG-1) is a cell adhesion molecule belonging to the immunoglobulin superfamily (IgSF). It has six immunoglobulin-like extracellular domains and four fibronectin III-like ones, with anchoring to the cell membrane through glycosylphosphatidyl inositol. Contactin-2/TAG-1 is expressed in specific neurons transiently on the axonal surface during the fetal period. In postnatal stages, Contactin-2/TAG-1 is expressed in cerebellar granule cells, hippocampal pyramidal cells, and the juxtaparanodal regions of myelinated nerve fibers...
January 31, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28131909/differential-gene-expression-by-1-25-oh-2d3-in-an-endometriosis-stromal-cell-line
#18
Sue Ann Ingles, Liang Wu, Benjamin T Liu, Yibu Chen, Chun-Yeh Wang, Claire Templeman, Doerthe Brueggmann
Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH)2D3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH)2D3, and RNA-seq was used to identify genes differentially expressed between treated and untreated cells...
January 28, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28130225/cellular-model-of-colon-cancer-progression-reveals-signatures-of-mrnas-mirna-lncrnas-and-epigenetic-modifications-associated-with-metastasis
#19
Matjaz Rokavec, David Horst, Heiko Hermeking
Here we developed and comprehensively characterized a cellular model of colon cancer progression consisting of four defined derivatives of a colon cancer cell line that resulted from consecutive epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT/MET) and phenotypically recapitulate the metastatic cascade. Initial EMT was induced by prolonged exposure to IL-6, a cytokine also generated by the tumor-stroma. Genome-wide characterization of transcriptional (mRNA, miRNA, lncRNA) and epigenetic (DNA methylation, H3K4me3, H3K79me3, and H3K27me3 histone modifications) profiles of the cell derivatives, combined with correlative analyses of expression, methylation, and clinical data from the TCGA-COAD database gave insights into the molecular basis of their phenotypic changes...
January 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/28127889/cell-free-artificial-implants-of-electrospun-fibres-in-a-three-dimensional-gelatin-matrix-support-sciatic-nerve-regeneration-in-vivo
#20
Andreas Kriebel, Dorothee Hodde, Thomas Kuenzel, Jessica Engels, Gary Brook, Jörg Mey
Surgical repair of larger peripheral nerve lesions requires the use of autologous nerve grafts. At present, clinical alternatives to avoid nerve transplantation consist of empty tubes, which are only suitable for the repair over short distances and have limited success. We developed a cell-free, three-dimensional scaffold for axonal guidance in long-distance nerve repair. Sub-micron scale fibres of biodegradable poly-ε-caprolactone (PCL) and collagen/PCL (c/PCL) blends were incorporated in a gelatin matrix and inserted in collagen tubes...
January 27, 2017: Journal of Tissue Engineering and Regenerative Medicine
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