المؤلفون: Tatsumi Hirata, Fumio Nakamura, Takahiko Kawasaki, Yuji Kurihara, Yoshio Goshima, Megumi Yamaguchi, Naoya Yamashita, Kohtaro Takei, Yasufumi Sato, Hiroshi Kiyonari, Masumi Iketani, Yuko Arie, Stephen M. Strittmatter, Takaya Abe

المصدر: Science. 333:769-773

مصطلحات موضوعية: Olfactory system, medicine.drug_class, Nogo Proteins, Growth Cones, Receptors, Cell Surface, Biology, GPI-Linked Proteins, Ligands, Article, Cell Line, Mice, Prosencephalon, Nogo Receptor 1, Calcium-binding protein, mental disorders, medicine, Biological neural network, Animals, Humans, Axon, Receptor, Growth cone, Cells, Cultured, Mice, Inbred ICR, Binding Sites, Multidisciplinary, Calcium-Binding Proteins, fungi, food and beverages, Olfactory Pathways, Receptor antagonist, Immunohistochemistry, Axons, Cell biology, medicine.anatomical_structure, Immunology, Signal transduction, Myelin Proteins, Protein Binding, Signal Transduction

الوصف: Neural circuitry formation depends on the molecular control of axonal projection during development. By screening with fluorophore-assisted light inactivation in the developing mouse brain, we identified cartilage acidic protein–1B as a key molecule for lateral olfactory tract (LOT) formation and named it LOT usher substance (LOTUS). We further identified Nogo receptor–1 (NgR1) as a LOTUS-binding protein. NgR1 is a receptor of myelin-derived axon growth inhibitors, such as Nogo, which prevent neural regeneration in the adult. LOTUS suppressed Nogo-NgR1 binding and Nogo-induced growth cone collapse. A defasciculated LOT was present in lotus-deficient mice but not in mice lacking both lotus- and ngr1. These findings suggest that endogenous antagonism of NgR1 by LOTUS is crucial for normal LOT formation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b76278cfa8b0874e36cb35e18ec164fTest
https://doi.org/10.1126Test/science.1204144

المؤلفون: Erik M. Jorgensen, Michael Bastiani, Paola Nix, Linda Hauth, Marc Hammarlund

المصدر: Science. 323:802-806

مصطلحات موضوعية: Aging, MAP Kinase Kinase 4, MAP Kinase Signaling System, medicine.medical_treatment, Growth Cones, Models, Biological, Article, medicine, Animals, Axon, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Growth cone, gamma-Aminobutyric Acid, Motor Neurons, Multidisciplinary, MAP kinase kinase kinase, biology, Regeneration (biology), Axotomy, Motor neuron, MAP Kinase Kinase Kinases, Axons, Nerve Regeneration, Cell biology, medicine.anatomical_structure, nervous system, Mitogen-activated protein kinase, Mutation, biology.protein, RNA Interference, Neuron, Mitogen-Activated Protein Kinases

الوصف: Regeneration of injured neurons can restore function, but most neurons regenerate poorly or not at all. The failure to regenerate in some cases is due to a lack of activation of cell-intrinsic regeneration pathways. These pathways might be targeted for the development of therapies that can restore neuron function after injury or disease. Here, we show that the DLK-1 mitogen-activated protein (MAP) kinase pathway is essential for regeneration in Caenorhabditis elegans motor neurons. Loss of this pathway eliminates regeneration, whereas activating it improves regeneration. Further, these proteins also regulate the later step of growth cone migration. We conclude that after axon injury, activation of this MAP kinase cascade is required to switch the mature neuron from an aplastic state to a state capable of growth.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::543500ce5902e37d9b98de05d5c84fddTest
https://doi.org/10.1126Test/science.1165527

المؤلفون: Ryuichi Nishinakamura, Sanbing Zhang, Iftekhar Bin Naser, Satomi S. Tanaka, Hiroshi Kiyonari, Sandy Chen, Toshio Terashima, Giasuddin Ahmed, Takaya Abe, Hideaki Tanaka, Shahidul M. Islam, Tatsuya Okafuji, Yohei Shinmyo, Kunimasa Ohta, Yuhong Su, Toshio Kitamura

المصدر: Science. 323:388-393

مصطلحات موضوعية: Nervous system, Neurite, Neurogenesis, Growth Cones, Molecular Sequence Data, Chick Embryo, Biology, Corpus Callosum, Tissue Culture Techniques, Mice, Prosencephalon, Chlorocebus aethiops, Neurites, Forebrain Commissures, medicine, Animals, Amino Acid Sequence, Mice, Knockout, Multidisciplinary, Anatomy, Commissure, Spinal cord, Axons, Coculture Techniques, Recombinant Proteins, Electroporation, medicine.anatomical_structure, Spinal Cord, nervous system, COS Cells, Knockout mouse, Intercellular Signaling Peptides and Proteins, Axon guidance, Neuroglia, Neuroscience

الوصف: Axon guidance proteins are critical for the correct wiring of the nervous system during development. Several axon guidance cues and their family members have been well characterized. More unidentified axon guidance cues are assumed to participate in the formation of the extremely complex nervous system. We identified a secreted protein, draxin, that shares no homology with known guidance cues. Draxin inhibited or repelled neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Ectopically expressed draxin inhibited growth or caused misrouting of chick spinal cord commissural axons in vivo. draxin knockout mice showed defasciculation of spinal cord commissural axons and absence of all forebrain commissures. Thus, draxin is a previously unknown chemorepulsive axon guidance molecule required for the development of spinal cord and forebrain commissures.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::300e9be44b4c1b207c89ff35eabf2139Test
https://doi.org/10.1126Test/science.1165187

المؤلفون: David J. Odde, Clarence E. Chan

المصدر: Science. 322:1687-1691

مصطلحات موضوعية: Materials science, medicine.medical_treatment, Growth Cones, Nanotechnology, Chick Embryo, macromolecular substances, Models, Biological, Elastic Modulus, Cell Adhesion, medicine, Animals, Surface Tension, Computer Simulation, Pseudopodia, Elastic modulus, Cells, Cultured, Myosin Type II, Neurons, Multidisciplinary, Durotaxis, Dynamics (mechanics), Stiffness, Mechanics, Elasticity (physics), Traction (orthopedics), Actins, Elasticity, Biomechanical Phenomena, Actin Cytoskeleton, Slippage, medicine.symptom, Filopodia, Compliance

الوصف: Cells sense the environment's mechanical stiffness to control their own shape, migration, and fate. To better understand stiffness sensing, we constructed a stochastic model of the “motor-clutch” force transmission system, where molecular clutches link F-actin to the substrate and mechanically resist myosin-driven F-actin retrograde flow. The model predicts two distinct regimes: (i) “frictional slippage,” with fast retrograde flow and low traction forces on stiff substrates and (ii) oscillatory “load-and-fail” dynamics, with slower retrograde flow and higher traction forces on soft substrates. We experimentally confirmed these model predictions in embryonic chick forebrain neurons by measuring the nanoscale dynamics of single–growth-cone filopodia. Furthermore, we experimentally observed a model-predicted switch in F-actin dynamics around an elastic modulus of 1 kilopascal. Thus, a motor-clutch system inherently senses and responds to the mechanical stiffness of the local environment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d1615f2a1943a6ffd2d7e918ea750ea2Test
https://doi.org/10.1126Test/science.1163595

المؤلفون: Wilfried Rossoll, Sandra Kröber, Christine E. Beattie, Michael Krawczak, Michelle L. McWhorter, Gary J. Bassell, Stefan Müller, Brunhilde Wirth, Gabriela E. Oprea

المصدر: Science. 320:524-527

مصطلحات موضوعية: Male, medicine.medical_specialty, Transcription, Genetic, Growth Cones, Gene Expression, Nerve Tissue Proteins, SMN1, Biology, Axonogenesis, Article, Cell Line, Muscular Atrophy, Spinal, Mice, Internal medicine, medicine, PLS3, Animals, Humans, Axon, Cyclic AMP Response Element-Binding Protein, Zebrafish, Genetics, Membrane Glycoproteins, Multidisciplinary, Microfilament Proteins, RNA-Binding Proteins, Cell Differentiation, SMN Complex Proteins, Spinal muscular atrophy, Motor neuron, Phosphoproteins, medicine.disease, SMA, biology.organism_classification, Survival of Motor Neuron 1 Protein, Actins, Axons, nervous system diseases, Pedigree, medicine.anatomical_structure, Endocrinology, Spinal Cord, Female

الوصف: Homozygous deletion of the survival motor neuron 1 gene ( SMN1 ) causes spinal muscular atrophy (SMA), the most frequent genetic cause of early childhood lethality. In rare instances, however, individuals are asymptomatic despite carrying the same SMN1 mutations as their affected siblings, thereby suggesting the influence of modifier genes. We discovered that unaffected SMN1 -deleted females exhibit significantly higher expression of plastin 3 ( PLS3 ) than their SMA-affected counterparts. We demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN down-regulation in motor neurons of SMA mouse embryos and in zebrafish. Our study suggests that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5f2ea718a7f942307ea90f0aed1d4d2Test
https://doi.org/10.1126Test/science.1155085

المؤلفون: Michela Matteoli, Yuchio Yanagawa, Ann M. Rajnicek, Andrew J. Irving, Krisztina Monory, Beat Lutz, Ken Mackie, Yury M. Morozov, Jan Mulder, Pasko Rakic, Alison J. Canty, István Katona, Giovanni Marsicano, Paul Berghuis, Gabriella M. Urbán, Tibor Harkany, Ruth A. Ross

المصدر: Science. 316:1212-1216

مصطلحات موضوعية: medicine.medical_specialty, Cannabinoid receptor, Growth Cones, Synaptogenesis, Xenopus Proteins, Biology, Rats, Sprague-Dawley, Mice, Xenopus laevis, Receptor, Cannabinoid, CB1, Chemorepulsion, Cell Movement, Interneurons, Internal medicine, Cannabinoid Receptor Modulators, medicine, Animals, Axon, Growth cone, Cells, Cultured, In Situ Hybridization, gamma-Aminobutyric Acid, Ultrasonography, Cerebral Cortex, Microscopy, Confocal, Multidisciplinary, Stem Cells, musculoskeletal, neural, and ocular physiology, Endocannabinoid system, Axons, Rats, Mice, Inbred C57BL, Endocrinology, medicine.anatomical_structure, nervous system, Synapses, GABAergic, lipids (amino acids, peptides, and proteins), Axon guidance, Neuroscience, Endocannabinoids, Signal Transduction

الوصف: The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB 1 cannabinoid receptors (CB 1 Rs) are enriched in the axonal growth cones of γ-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB 1 R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB 1 Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18b7bb4179747c67682e1fcaa7dac66eTest
https://doi.org/10.1126Test/science.1137406

المؤلفون: Antonio Colavita, Marc Tessier-Lavigne

المصدر: Science. 302:293-296

مصطلحات موضوعية: Nervous system, Recombinant Fusion Proteins, Growth Cones, Molecular Sequence Data, Neurexin, Ligands, Vulva, Animals, Genetically Modified, Protein structure, medicine, Animals, Amino Acid Sequence, Axon, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Promoter Regions, Genetic, Genes, Helminth, Motor Neurons, Multidisciplinary, biology, Gene Expression Profiling, Membrane Proteins, Anatomy, biology.organism_classification, Axons, Transmembrane protein, Protein Structure, Tertiary, Cell biology, medicine.anatomical_structure, nervous system, Mutation, Female, Ectopic expression, Neuron, Cues

الوصف: Neuronal axons connect to multiple target cells through the formation of collateral branches, but the mechanisms that regulate this process are largely unknown. We show that BAM-2, a neurexin-related transmembrane protein, is required for development of VC motoneuron branches in the worm Caenorhabditis elegans . Expression analysis and ectopic expression experiments suggest that BAM-2 functions as a branch termination cue and reveal a mechanism for selective control of branches that sprout off a primary axon.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::40e3fbf2342a654af1f9d0797732ef1dTest
https://doi.org/10.1126Test/science.1089163

المؤلفون: Leslie Pick, Ronald A. Kohanski, Zun Chen, Lingling Wu, Jianbo Song

المصدر: Science. 300:502-505

مصطلحات موضوعية: Male, medicine.medical_specialty, medicine.medical_treatment, Blotting, Western, Growth Cones, Nerve Tissue Proteins, Biology, Eye, Retina, src Homology Domains, Two-Hybrid System Techniques, Internal medicine, Insulin receptor substrate, medicine, Animals, Drosophila Proteins, Visual Pathways, Axon, Growth cone, Receptor, Adaptor Proteins, Signal Transducing, Cell Size, Binding Sites, Multidisciplinary, Insulin, Intracellular Signaling Peptides and Proteins, Brain, Receptor Protein-Tyrosine Kinases, Signal transducing adaptor protein, Cell Differentiation, Protein-Tyrosine Kinases, Precipitin Tests, Axons, Receptor, Insulin, Cell biology, Insulin receptor, medicine.anatomical_structure, Endocrinology, Mutation, Insulin Receptor Substrate Proteins, biology.protein, Drosophila, Female, Photoreceptor Cells, Invertebrate, Axon guidance, Carrier Proteins, Signal Transduction

الوصف: Insulin receptors are abundant in the central nervous system, but their roles remain elusive. Here we show that the insulin receptor functions in axon guidance. The Drosophila insulin receptor (DInR) is required for photoreceptor-cell (R-cell) axons to find their way from the retina to the brain during development of the visual system. DInR functions as a guidance receptor for the adapter protein Dock/Nck. This function is independent of Chico, the Drosophila insulin receptor substrate (IRS) homolog.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1dfa3e28e8738aa2fc8e93ef66822dbaTest
https://doi.org/10.1126Test/science.1081203

المؤلفون: Timothy M. Gomez, Mu-ming Poo, Nicholas C. Spitzer, Estuardo Robles

المصدر: Science. 291:1983-1987

مصطلحات موضوعية: Integrins, Embryo, Nonmammalian, Neurite, Xenopus, Growth Cones, Motility, Biology, Calcium in biology, Cell Movement, Culture Techniques, Neurites, medicine, Extracellular, Animals, Calcium Signaling, Pseudopodia, Growth cone, Cells, Cultured, Neurons, Microscopy, Confocal, Multidisciplinary, Integrin beta1, Tenascin, Anatomy, medicine.anatomical_structure, Biophysics, Calcium, Laminin, Neuron, Signal transduction, Oligopeptides, Filopodia

الوصف: Filopodia that extend from neuronal growth cones sample the environment for extracellular guidance cues, but the signals they transmit to growth cones are unknown. Filopodia were observed generating localized transient elevations of intracellular calcium ([Ca2+]i) that propagate back to the growth cone and stimulate global Ca2+elevations. The frequency of filopodial Ca2+transients was substrate-dependent and may be due in part to influx of Ca2+through channels activated by integrin receptors. These transients slowed neurite outgrowth by reducing filopodial motility and promoted turning when stimulated differentially within filopodia on one side of the growth cone. These rapid signals appear to serve both as autonomous regulators of filopodial movement and as frequency-coded signals integrated within the growth cone and could be a common signaling process for many motile cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::80cea4eac615be333583a3081f9efb48Test
https://doi.org/10.1126Test/science.1056490

المؤلفون: John G. Flanagan, E. Yvonne Jones, Geoffrey C. Sutton, John T. Gallagher, A. Radu Aricescu, Yingjie Shen, C.H. Coles, Christian Siebold, Alan P. Tenney, W. Lu

المصدر: Coles, C H, Shen, Y, Tenney, A P, Siebold, C, Sutton, G C, Lu, W, Gallagher, J T, Jones, E Y, Flanagan, J G & Aricescu, A 2011, ' Proteoglycan-Specific Molecular Switch for RPTPσ Clustering and Neuronal Extension ', Science, vol. 332, no. 6028, pp. 484-488 . https://doi.org/10.1126Test/science.1200840

مصطلحات موضوعية: Models, Molecular, animal structures, Sensory Receptor Cells, Neurite, Protein Conformation, Growth Cones, Molecular Sequence Data, Crystallography, X-Ray, Models, Biological, Article, Mice, chemistry.chemical_compound, Glypicans, Neurocan, Ganglia, Spinal, Neurites, medicine, Animals, Humans, Amino Acid Sequence, Chondroitin sulfate, Growth cone, Cells, Cultured, Binding Sites, Multidisciplinary, biology, Cell Membrane, Chondroitin Sulfates, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Heparan sulfate, Axons, Sensory neuron, Extracellular Matrix, Protein Structure, Tertiary, Cell biology, carbohydrates (lipids), medicine.anatomical_structure, Chondroitin Sulfate Proteoglycans, chemistry, Ectodomain, Proteoglycan, Biochemistry, biology.protein, Heparitin Sulfate, Protein Multimerization, Heparan Sulfate Proteoglycans

الوصف: Heparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) regulate numerous cell surface signaling events, with typically opposite effects on cell function. CSPGs inhibit nerve regeneration through receptor protein tyrosine phosphatase sigma (RPTPs). Here we report that RPTPs acts bimodally in sensory neuron extension, mediating CSPG inhibition and HSPG growth promotion. Crystallographic analyses of a shared HSPG-CSPG binding site reveal a conformational plasticity that can accommodate diverse glycosaminoglycans with comparable affinities. Heparan sulfate and analogs induced RPTPs ectodomain oligomerization in solution, which was inhibited by chondroitin sulfate. RPTPs and HSPGs colocalize in puncta on sensory neurons in culture, whereas CSPGs occupy the extracellular matrix. These results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efd47b622749a302dc7c3b9c0782f02dTest
http://ora.ox.ac.uk/objects/uuid:0bbb31a5-7206-456c-a5c4-47ad6ec59ff3Test