المؤلفون: Camilla B. Mitchell, Holly Hardy, Lisa Foa, John K. Chilton, Kaylene M. Young, Adrian C. Thompson, Robert Gasperini, Macarena Pavez

المصدر: Molecular and Cellular Neuroscience. 84:29-35

مصطلحات موضوعية: 0301 basic medicine, Nervous system, Growth Cones, Motility, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Cell Movement, medicine, Biological neural network, Animals, Humans, Growth cone, Molecular Biology, Cytoskeleton, Calcium signaling, Voltage-dependent calcium channel, Cell Biology, Axons, Sensory neuron, Axon Guidance, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Calcium, Axon guidance, Neuroscience, 030217 neurology & neurosurgery

الوصف: The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e52d3b38ef200630f0b2052ca8006604Test
https://doi.org/10.1016/j.mcn.2017.07.006Test

المؤلفون: Karl D. Bellve, Clive Standley, Zheng-Zheng Bao, Daorong Guo, Kevin E. Fogarty

المصدر: Molecular and Cellular Neuroscience. 50:82-92

مصطلحات موضوعية: Retinal Ganglion Cells, Threonine, Protein Kinase C-alpha, animal structures, Growth Cones, Optic disk, Chick Embryo, Protein Serine-Threonine Kinases, Article, Cellular and Molecular Neuroscience, Animals, Benzopyrans, Hedgehog Proteins, Integrin-linked kinase, Enzyme Inhibitors, Phosphorylation, Sonic hedgehog, Growth cone, Protein kinase A, Molecular Biology, Cells, Cultured, biology, Acetophenones, Cell Biology, Molecular biology, Axons, Cell biology, Mutation, embryonic structures, biology.protein, Calcium, Axon guidance, sense organs, Signal transduction, Morphogen

الوصف: In addition to its role as a morphogen, Sonic hedgehog (Shh) has also been shown to function as a guidance factor that directly acts on the growth cones of various types of axons. However, the noncanonical signaling pathways that mediate the guidance effects of Shh protein remain poorly understood. We demonstrate that a novel signaling pathway consisting of protein kinase Cα (PKCα) and integrin-linked kinase (ILK) mediates the negative guidance effects of high concentration of Shh on retinal ganglion cell (RGC) axons. Shh rapidly increased Ca(2+) level and activated PKCα and ILK in the growth cones of RGC axons. By in vitro kinase assay, PKCα was found to directly phosphorylate ILK on threonine-173 and -181. Inhibition of PKCα or expression of a mutant ILK with the PKCα phosphorylation sites mutated (ILK-DM), abolished the Shh-induced macropinocytosis, growth cone collapse and repulsive axon turning. In vivo, expression of a dominant negative PKCα or ILK-DM disrupted RGC axon pathfinding at the optic chiasm but not the projection toward the optic disk, supporting that this signaling pathway plays a specific role in Shh-mediated negative guidance effects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47376f0b9d0d332d3f025febb245491cTest
https://doi.org/10.1016/j.mcn.2012.03.008Test

المؤلفون: Tiago Bandeira de Lima, John K. Chilton, James A. Van Allen, Xin-Peng Dun, Phillip R. Gordon-Weeks, Sara Geraldo

المصدر: Molecular and Cellular Neurosciences

مصطلحات موضوعية: Nervous system, Cell type, Cellular differentiation, Growth Cones, Biology, Article, Cellular and Molecular Neuroscience, Cell Movement, medicine, Actin-binding, Pseudopodia, Cytoskeleton, Growth cone, Molecular Biology, Migration, Neurons, PCN, precerebellar nuclei, OMN, oculomotor nucleus, Microfilament Proteins, Neuropeptides, Cell Differentiation, Cell Biology, Anatomy, Motor neuron, Axons, YFP, yellow fluorescent protein, medicine.anatomical_structure, Leading process, Axon guidance, Drebrin, Neuroscience, Oculomotor

الوصف: article Formation of a functional nervous system requiresneurons to migrate to the correct place withinthe developing brain. Tangentially migrating neurons are guided by a leading process which extends towards the target and is followed by the cell body. How environmental cues are coupled to specific cytoskeletal changes to produce and guide leading process growth is unknown. One such cytoskeletal modulator is drebrin, an actin-binding protein known to induce protrusions in many cell types and be important for regulating neuronal morphology. Using the migration of oculomotor neurons as a model, we have shown that drebrin is necessary for the gener- ation and guidance of the leading process. In the absence of drebrin, leading processes are not formed and cells fail to migrate although axon growth and pathfinding appear grossly unaffected. Conversely, when levels of drebrin are elevated the leading processes turn away from their target and as a result the motor neuron cell bodies move along abnormal paths within the brain. The aberrant trajectories were highly reproducible suggest- ing that drebrin is required to interpret specific guidance cues. The axons and growth cones of these neurons display morphological changes, particularly increased branching and filopodial number but despite this they extend along normal developmental pathways. Collectively these results show that drebrin is initially necessary for the formation of a leading process and sub- sequently for this to respond to navigational signals and grow in the correct direction. Furthermore, we have shown that the actions of drebrin can be segregated within individual motor neurons to direct their migration independently of axon guidance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c22328f2de54c8557aca1acbfe369197Test
https://doi.org/10.1016/j.mcn.2012.01.006Test

المؤلفون: Linda J. Richards, Zac Pujic, Geoffrey J. Goodhill, Andrew W. Thompson

المصدر: Molecular and Cellular Neuroscience. 47:45-52

مصطلحات موضوعية: Nervous system, Superior cervical ganglion, Growth Cones, Cell Culture Techniques, Superior Cervical Ganglion, Biology, Cellular and Molecular Neuroscience, Cyclic nucleotide, chemistry.chemical_compound, Cell Movement, Nerve Growth Factor, Cyclic GMP-Dependent Protein Kinases, medicine, Animals, Rats, Wistar, Growth cone, Molecular Biology, Cells, Cultured, Cell Biology, Cyclic AMP-Dependent Protein Kinases, Axons, Rats, medicine.anatomical_structure, Nerve growth factor, chemistry, Axon guidance, Nucleotides, Cyclic, Neuroscience

الوصف: Correct wiring of the nervous system during development requires axons to respond appropriately to gradients of attractive and repulsive guidance cues. However, the steepness and concentration of these gradients vary in vivo, for instance, with distance from the target. Understanding how these changing conditions affect the navigation strategies used by developing axons is important for understanding how they are guided over long distances. Previous work has shown that cyclic nucleotide levels determine whether axons are attracted or repelled by steep gradients of the same guidance cue, but it is unknown whether this is also true for shallow gradients. We therefore investigated the guidance responses of rat superior cervical ganglion (SCG) axons in both steep and shallow gradients of nerve growth factor (NGF). In steep gradients we found that cyclic nucleotide-dependent switching occurred, consistent with previous reports. Surprisingly however, we found that in shallow NGF gradients, cyclic nucleotide-dependent switching did not occur. These results suggest that there may be substantial differences in the way axons respond to gradient-based guidance cues depending on where they are within the gradient.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf8d24ce73089c3ccdf8f387c8c04ecfTest
https://doi.org/10.1016/j.mcn.2011.02.012Test

المؤلفون: Susann M Brady-Kalnay, Samantha A. Oblander

المصدر: Molecular and Cellular Neuroscience. 44:78-93

مصطلحات موضوعية: rac1 GTP-Binding Protein, Cell signaling, Neurite, Neurogenesis, Growth Cones, Chick Embryo, CDC42, Biology, Article, Retina, Cellular and Molecular Neuroscience, IQGAP1, Neurites, Animals, Growth cone, Molecular Biology, Cells, Cultured, Protein Kinase C, Cadherin, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Cell Differentiation, Cell Biology, Cadherins, Cell biology, Axon guidance, Signal transduction, Neuroscience, Signal Transduction

الوصف: Classical cadherins play distinct roles in axon growth and guidance in the visual system, however, the signaling pathways they activate remain unclear. Growth cones on each cadherin substrate have a unique morphology suggesting that distinct signals are activated by neurite outgrowth on E-, N-, and R-cadherin. We previously demonstrated that receptor protein tyrosine phosphatase-mu (PTPmu) is required for E- and N-cadherin-dependent neurite outgrowth. In this manuscript, we demonstrate that PTPmu regulates R-cadherin-mediated neurite outgrowth. Furthermore, we evaluated whether known PTPmu-associated signaling proteins, Rac1, Cdc42, IQGAP1 and PKCδ, regulate neurite outgrowth mediated by these cadherins. While Rac1 activity is required for neurite outgrowth on all three cadherins Cdc42/IQGAP1 are required only for N- and R-cadherin-mediated neurite outgrowth. In addition, we determined that PKC activity is required for E- and R-cadherin-mediated, but not N-cadherin-mediated neurite outgrowth. In summary, distinct PTPµ-associated signaling proteins are required to promote neurite outgrowth on cadherins.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1852e9b02a058914e2ea42adaef6c056Test
https://doi.org/10.1016/j.mcn.2010.02.005Test

المؤلفون: Scott E. Williams, Timothy J. Petros, Carol A. Mason

المصدر: Molecular and Cellular Neuroscience. 32:49-66

مصطلحات موضوعية: Retinal Ganglion Cells, Time Factors, genetic structures, Growth Cones, Down-Regulation, Cell Communication, Biology, Retina, Mice, Cellular and Molecular Neuroscience, Organ Culture Techniques, Cell Movement, medicine, Animals, Ephrin, Optic stalk, Molecular Biology, Mice, Knockout, Stem Cells, Receptor, EphA4, Erythropoietin-producing hepatocellular (Eph) receptor, Gene Expression Regulation, Developmental, Cell Differentiation, Optic Nerve, Cell Biology, eye diseases, medicine.anatomical_structure, Retinal ganglion cell, Astrocytes, Optic nerve, Axon guidance, sense organs, Neuroscience, Optic disc

الوصف: Eph receptors and their ephrin ligands play important roles in many aspects of visual system development. In this study, we characterized the spatial and temporal expression pattern of EphA4 in astrocyte precursor cell (APC) and astrocyte populations in the murine retina and optic nerve. EphA4 is expressed by immotile optic disc astrocyte precursor cells (ODAPS), but EphA4 is downregulated as these cells migrate into the retina. Surprisingly, mature astrocytes in the adult retina re-express EphA4. Within the optic nerve, EphA4 is expressed in specialized astrocytes that form a meshwork at the optic nerve head (ONH). Our in vitro and in vivo data indicate that EphA4 is dispensable for retinal ganglion cell (RGC) axon growth and projections through the chiasm. While optic stalk structure, APC proliferation and migration, retinal vascularization, and oligodendrocyte migration appear normal in EphA4 mutants, the expression of EphA4 in APCs and in the astrocyte meshwork at the ONH has implications for optic nerve pathologies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21c99d1b6c0be45055563ca3a6da1de0Test
https://doi.org/10.1016/j.mcn.2006.02.002Test

المؤلفون: Susann M. Brady-Kalnay, Sonya E. Ensslen-Craig

المصدر: Molecular and Cellular Neuroscience. 28:177-188

مصطلحات موضوعية: Retinal Ganglion Cells, animal structures, Neurite, Cellular differentiation, Growth Cones, Cell Communication, Chick Embryo, Protein tyrosine phosphatase, Biology, environment and public health, Catalysis, Retina, Cellular and Molecular Neuroscience, Organ Culture Techniques, Catalytic Domain, medicine, Animals, Receptor-Like Protein Tyrosine Phosphatases, Class 8, Growth cone, Molecular Biology, Cell adhesion molecule, Receptor-Like Protein Tyrosine Phosphatases, Class 2, Cell Differentiation, Cell Biology, Rats, Cell biology, enzymes and coenzymes (carbohydrates), medicine.anatomical_structure, Retinal ganglion cell, Axon guidance, Cues, Protein Tyrosine Phosphatases, Visual Fields, Neuroscience, Neural development, Protein Binding

الوصف: Cell adhesion molecules (CAMs) regulate neural development via both homophilic and heterophilic binding interactions. Various members of the receptor protein tyrosine phosphatase (RPTP) subfamily of CAMs mediate neurite outgrowth, yet in many cases, their ligands remain unknown. However, the PTP mu subfamily members are homophilic binding proteins. PTP mu is a growth-permissive substrate for nasal retinal ganglion cell (RGC) neurites and a growth inhibitory substrate for temporal RGC neurites. Whether PTP mu regulates these distinct behaviors via homophilic or heterophilic binding interactions is not currently known. In this manuscript, we demonstrate that PTP mu influences RGC axon guidance behaviors only in the E8 retina and not earlier in development. In addition, we demonstrate that PTP mu is permissive only for neurites from ventral-nasal retina and is repulsive to neurites from all other retinal quadrants. Furthermore, we show that PTP mu-mediated nasal neurite outgrowth and temporal repulsion require PTP mu expression and catalytic activity. These results are consistent with PTP mu homophilic binding generating a tyrosine phosphatase-dependent signal that ultimately leads to axon outgrowth or repulsion and that PTP mu's role in regulating axon guidance may be tightly regulated developmentally. In summary, these data demonstrate that PTP mu expression and catalytic activity are important in vertebrate axon guidance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a09ed0473ef37bef8df479663ea5bf5bTest
https://doi.org/10.1016/j.mcn.2004.08.011Test

المؤلفون: E. David Litwack, Reto Buser, Matthias Gesemann, Dennis D.M. O'Leary, Regis Babey

المصدر: Molecular and Cellular Neuroscience. 25:263-274

مصطلحات موضوعية: Central Nervous System, Nervous system, DNA, Complementary, Glycosylation, Growth Cones, Molecular Sequence Data, Immunoglobulins, Hindbrain, Biology, GPI-Linked Proteins, Nervous System, Cellular and Molecular Neuroscience, Fetus, Cell Movement, Pons, Peripheral Nervous System, medicine, Animals, Amino Acid Sequence, Nerve Growth Factors, Neural Cell Adhesion Molecules, Molecular Biology, Membrane Glycoproteins, Base Sequence, Sequence Homology, Amino Acid, Gene Expression Regulation, Developmental, Membrane Proteins, Cell Differentiation, Cell Biology, Protein Structure, Tertiary, Rats, Olfactory bulb, medicine.anatomical_structure, nervous system, Immunoglobulin superfamily, Axon guidance, MDGA2, Neural development, Nucleus, Neuroscience

الوصف: We recently used a differential display PCR screen to identify secreted and transmembrane proteins that are highly expressed in the developing rat basilar pons, a prominent ventral hindbrain nucleus used as a model for studies of neuronal migration, axon outgrowth, and axon-target recognition. Here we describe cloning and characterization of one of these molecules, now called MDGA1, and a closely related homologue, MDGA2. Analyses of the full-length coding region of MDGA1 and MDGA2 indicate that they encode proteins that comprise a novel subgroup of the Ig superfamily and have a unique structural organization consisting of six immunoglobulin (Ig)-like domains followed by a single MAM domain. Biochemical characterization demonstrates that MDGA1 and MDGA2 proteins are highly glycosylated, and that MDGA1 is tethered to the cell membrane by a GPI anchor. The MDGAs are differentially expressed by subpopulations of neurons in both the central and peripheral nervous systems, including neurons of the basilar pons, inferior olive, cerebellum, cerebral cortex, olfactory bulb, spinal cord, and dorsal root and trigeminal ganglia. Little or no MDGA expression is detected outside of the nervous system of developing rats. The similarity of MDGAs to other Ig-containing molecules and their temporal-spatial patterns of expression within restricted neuronal populations, for example migrating pontine neurons and D1 spinal interneurons, suggest a role for these novel proteins in regulating neuronal migration, as well as other aspects of neural development, including axon guidance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08b226f93c67ad6ce197e5fb17905ba7Test
https://doi.org/10.1016/j.mcn.2003.10.016Test