المؤلفون: Bo T. Porse, Samie R. Jaffrey, Sheng-Jian Ji, Dilek Colak

المصدر: Cell. 153:1252-1265

مصطلحات موضوعية: Cell signaling, Growth Cones, Nonsense-mediated decay, Nerve Tissue Proteins, Receptors, Cell Surface, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Protein biosynthesis, Animals, Growth cone, 030304 developmental biology, Floor plate, 0303 health sciences, Biochemistry, Genetics and Molecular Biology(all), Membrane Proteins, Translation (biology), Embryo, Mammalian, Slit, Molecular biology, Axons, Nonsense Mediated mRNA Decay, Cell biology, Spinal Cord, nervous system, Axon guidance, 030217 neurology & neurosurgery

الوصف: SummaryGrowth cones enable axons to navigate toward their targets by responding to extracellular signaling molecules. Growth-cone responses are mediated in part by the local translation of axonal messenger RNAs (mRNAs). However, the mechanisms that regulate local translation are poorly understood. Here we show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3.2 expression. These data show that local translation is regulated by mRNA stability and that NMD acts locally to influence axonal pathfinding.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c42467240f17210964fd7b57e546b597Test
https://doi.org/10.1016/jTest.cell.2013.04.056

المؤلفون: Vicky Yamamoto, Blanca Ortega, Wange Lu, David Baltimore

المصدر: Cell. 119:97-108

مصطلحات موضوعية: Central Nervous System, Frizzled, Dishevelled Proteins, Receptor tyrosine kinase, Receptors, G-Protein-Coupled, Mice, 0302 clinical medicine, Genes, Regulator, Drosophila Proteins, RNA, Small Interfering, Receptor, chemistry.chemical_classification, 0303 health sciences, biology, Wnt signaling pathway, Cell Differentiation, Receptors, Neurotransmitter, Dishevelled, Cell biology, DNA-Binding Proteins, medicine.anatomical_structure, Protein Binding, Neurite, Lymphoid Enhancer-Binding Factor 1, Macromolecular Substances, T cell, Growth Cones, Mice, Transgenic, Wnt1 Protein, General Biochemistry, Genetics and Molecular Biology, Cell Line, Wnt3 Protein, 03 medical and health sciences, Proto-Oncogene Proteins, Wnt3A Protein, medicine, Animals, Humans, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Biochemistry, Genetics and Molecular Biology(all), Proteins, Receptor Protein-Tyrosine Kinases, Embryo, Mammalian, Phosphoproteins, Frizzled Receptors, Protein Structure, Tertiary, Wnt Proteins, chemistry, biology.protein, Axon guidance, 030217 neurology & neurosurgery, Transcription Factors

الوصف: The Ryk receptor belongs to the atypical receptor tyrosine kinase family. It is a new member of the family of Wnt receptor proteins. However, the molecular mechanisms by which the Ryk receptor functions remain unknown. Here, we report that mammalian Ryk, unlike the Drosophila Ryk homolog Derailed, functions as a coreceptor along with Frizzled for Wnt ligands. Ryk also binds to Dishevelled, through which it activates the canonical Wnt pathway, providing a link between Wnt and Dishevelled. Transgenic mice expressing Ryk siRNA exhibit defects in axon guidance, and Ryk is required for neurite outgrowth induced by Wnt-3a and in the activation of T cell factor (TCF) induced by Wnt-1. Thus, Ryk appears to play a crucial role in Wnt-mediated signaling.

وصف الملف: image/jpeg

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4fb66b851475b1a635cbba4de7fdcb05Test
https://doi.org/10.1016/jTest.cell.2004.09.019

المؤلفون: Peter Mombaerts, Paul Feinstein

المصدر: Cell. 117(6):817-831

مصطلحات موضوعية: Olfactory system, Growth Cones, Sensory system, Mice, Transgenic, Cell Communication, Biology, Receptors, Odorant, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Olfactory Receptor Neurons, Mice, Open Reading Frames, Animals, Amino Acid Sequence, Peptide sequence, chemistry.chemical_classification, Polymorphism, Genetic, Biochemistry, Genetics and Molecular Biology(all), Cell Membrane, Gene targeting, Gene Expression Regulation, Developmental, Cell Differentiation, Anatomy, Olfactory Bulb, Olfactory bulb, Amino acid, Protein Structure, Tertiary, Transmembrane domain, Phenotype, nervous system, chemistry, Gene Targeting, Synapses, Axon guidance, Neuroscience

الوصف: No models fully account for how odorant receptors (ORs) function in the guidance of axons of olfactory sensory neurons (OSNs) to glomeruli in the olfactory bulb. Here, we use gene targeting in mice to demonstrate that the OR amino acid sequence imparts OSN axons with an identity that allows them to coalesce into glomeruli. Replacements between the coding regions of the M71 and M72 OR genes reroute axons to their respective glomeruli. A series of M71-M72 hybrid ORs uncover a spectrum of glomerular phenotypes, leading to the concept that the identity of OSN axons is revealed depending on what other axons are present. Naturally occurring amino acid polymorphisms in other ORs also produce distinct axonal identities. These critical amino acid residues are distributed throughout the protein and reside predominantly within transmembrane domains. We propose a contextual model for axon guidance in which ORs mediate homotypic interactions between like axons.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c1c6c7809f2891f2494093ab247e721Test

المؤلفون: Juhee Jeong, Andrew P. McMahon, Marc Tessier-Lavigne, Elke Stein, Frédéric Charron

المصدر: Cell. 113:11-23

مصطلحات موضوعية: animal structures, Cell Adhesion Molecules, Neuronal, Growth Cones, Receptors, Cell Surface, Cell Communication, Biology, General Biochemistry, Genetics and Molecular Biology, Receptors, G-Protein-Coupled, Mice, Viral Proteins, Xenopus laevis, Fetus, Proto-Oncogene Proteins, Netrin, Contactin 2, Animals, Hedgehog Proteins, Nerve Growth Factors, Sonic hedgehog, Chemoattractant activity, Growth cone, Floor plate, Integrases, Biochemistry, Genetics and Molecular Biology(all), Chemotaxis, Tumor Suppressor Proteins, Veratrum Alkaloids, Cell Differentiation, Anatomy, Netrin-1, Zebrafish Proteins, Smoothened Receptor, Mice, Mutant Strains, Rats, Cell biology, Wnt Proteins, Spinal Cord, nervous system, COS Cells, embryonic structures, Trans-Activators, biology.protein, Axon guidance, Smoothened, Morphogen

الوصف: Developing axons are guided to their targets by attractive and repulsive guidance cues. In the embryonic spinal cord, the floor plate chemoattractant Netrin-1 is required to guide commissural neuron axons to the midline. However, genetic evidence suggests that other chemoattractant(s) are also involved. We show that the morphogen Sonic hedgehog (Shh) can mimic the additional chemoattractant activity of the floor plate in vitro and can act directly as a chemoattractant on isolated axons. Cyclopamine-mediated inhibition of the Shh signaling mediator Smoothened (Smo) or conditional inactivation of Smo in commissural neurons indicate that Smo activity is important for the additional chemoattractant activity of the floor plate in vitro and for the normal projection of commissural axons to the floor plate in vivo. These results provide evidence that Shh, acting via Smo, is a midline-derived chemoattractant for commissural axons and show that a morphogen can also act as an axonal chemoattractant.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ce9609d130be83b378d3dc97e47b0fdTest
https://doi.org/10.1016/s0092-8674Test(03)00199-5

المؤلفون: Irene Miguel-Aliaga, Stefan Thor, Douglas W. Allan, Susan E. St. Pierre

المصدر: Cell. 113(1):73-86

مصطلحات موضوعية: Central Nervous System, Growth Cones, LIM-Homeodomain Proteins, Neuropeptide, Receptors, Cell Surface, Cell Communication, Choristoma, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, medicine, Animals, Drosophila Proteins, FMRFamide, Transcription factor, Body Patterning, 030304 developmental biology, Homeodomain Proteins, Neurons, Regulation of gene expression, 0303 health sciences, Neuropeptide Gene, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Regulation, Developmental, Cell Differentiation, Zinc Fingers, Anatomy, Ganglia, Invertebrate, Cell biology, Drosophila melanogaster, medicine.anatomical_structure, Bone Morphogenetic Proteins, Mutation, Invertebrate embryology, Axon guidance, Neuron, 030217 neurology & neurosurgery, Signal Transduction, Transcription Factors

الوصف: Individual neurons express only one or a few of the many identified neurotransmitters and neuropeptides, but the molecular mechanisms controlling their selection are poorly understood. In the Drosophila ventral nerve cord, the six Tv neurons express the neuropeptide gene FMRFamide. Each Tv neuron resides within a neuronal cell group specified by the LIM-homeodomain gene apterous. We find that the zinc-finger gene squeeze acts in Tv cells to promote their unique axon pathfinding to a peripheral target. There, the BMP ligand Glass bottom boat activates the Wishful thinking receptor, initiating a retrograde BMP signal in the Tv neuron. This signal acts together with apterous and squeeze to activate FMRFamide expression. Reconstituting this “code,” by combined BMP activation and apterous/squeeze misexpression, triggers ectopic FMRFamide expression in peptidergic neurons. Thus, an intrinsic transcription factor code integrates with an extrinsic retrograde signal to select a specific neuropeptide identity within peptidergic cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f5f56edfb8ca0683b5eb6cf2eb6242c3Test

المؤلفون: Oswald Steward

المصدر: Cell. 110(5):537-540

مصطلحات موضوعية: genetic structures, Biochemistry, Genetics and Molecular Biology(all), Growth Cones, Membrane Proteins, Translation (biology), Anatomy, Biology, Axons, General Biochemistry, Genetics and Molecular Biology, Growth cone collapse, Protein Biosynthesis, Animals, Axon guidance, sense organs, Growth cone, Neuroscience, Signal Transduction

الوصف: Recent studies suggest that local translation of mRNA within axons plays a key role in two aspects of growth cone navigation. One line of evidence implies a local synthesis of proteins that mediate growth cone collapse and turning in response to guidance cues; another indicates that growth cones possess the machinery that would allow the local synthesis of receptors for axon guidance cues.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d980645fe8fa8e302f6b624eae12305Test

المؤلفون: Krystyna Keleman, Karin Paiha, David Teis, Barry J. Dickson, Srikanth Rajagopalan, Lukas A. Huber, Gerhard M. Technau, Diana Cleppien

المصدر: Cell. (4):415-427

مصطلحات موضوعية: Central Nervous System, Embryo, Nonmammalian, Endosome, Growth Cones, Molecular Sequence Data, Endocytic cycle, Down-Regulation, Nerve Tissue Proteins, Receptors, Cell Surface, Cell Communication, Endosomes, Biology, Models, Biological, Functional Laterality, General Biochemistry, Genetics and Molecular Biology, Sequence Homology, Nucleic Acid, Ectoderm, medicine, Animals, Drosophila Proteins, Receptors, Immunologic, Axon, Transport Vesicles, Receptor, Sequence Homology, Amino Acid, Biochemistry, Genetics and Molecular Biology(all), Stem Cells, Cell Membrane, Graft Survival, Gene Expression Regulation, Developmental, Membrane Proteins, Cell Differentiation, Anatomy, Commissure, Slit, Protein Structure, Tertiary, Cell biology, Protein Transport, Drosophila melanogaster, medicine.anatomical_structure, COS Cells, Roundabout, Axon guidance, Stem Cell Transplantation

الوصف: Axon growth across the Drosophila midline requires Comm to downregulate Robo, the receptor for the midline repellent Slit. We show here that comm is required in neurons, not in midline cells as previously thought, and that it is expressed specifically and transiently in commissural neurons. Comm acts as a sorting receptor for Robo, diverting it from the synthetic to the late endocytic pathway. A conserved cytoplasmic LPSY motif is required for endosomal sorting of Comm in vitro and for Comm to downregulate Robo and promote midline crossing in vivo. Axon traffic at the CNS midline is thus controlled by the intracellular trafficking of the Robo guidance receptor, which in turn depends on the precisely regulated expression of the Comm sorting receptor.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::649f7b11e71c13196dc014e6845cd699Test

المؤلفون: Huey Hing, Nicholas Harden, Louis Lim, S. Lawrence Zipursky, Jian Xiao

المصدر: Cell. (7):853-863

مصطلحات موضوعية: genetic structures, Recombinant Fusion Proteins, Growth Cones, Molecular Sequence Data, Nerve Tissue Proteins, macromolecular substances, Biology, Protein Serine-Threonine Kinases, General Biochemistry, Genetics and Molecular Biology, Cell membrane, GTP-binding protein regulators, GTP-Binding Proteins, medicine, Animals, Drosophila Proteins, Amino Acid Sequence, skin and connective tissue diseases, Cytoskeleton, Growth cone, Adaptor Proteins, Signal Transducing, Binding Sites, Biochemistry, Genetics and Molecular Biology(all), Cell Membrane, Signal transducing adaptor protein, eye diseases, Axons, Cell biology, rac GTP-Binding Proteins, Rac GTP-Binding Proteins, medicine.anatomical_structure, p21-Activated Kinases, Mutagenesis, Axon guidance, Drosophila, Photoreceptor Cells, Invertebrate, sense organs, Drosophila Protein

الوصف: The SH2/SH3 adaptor protein Dock has been proposed to transduce signals from guidance receptors to the actin cytoskeleton in Drosophila photoreceptor (R cell) growth cones. Here, we demonstrate that Drosophila p 21-a ctivated k inase (Pak) is required in a Dock pathway regulating R cell axon guidance and targeting. Dock and Pak colocalize to R cell axons and growth cones, physically interact, and their loss-of-function phenotypes are indistinguishable. Normal patterns of R cell connectivity require Pak’s kinase activity and binding sites for both Dock and Cdc42/Rac. A membrane-tethered form of Pak (Pakmyr) acts as a dominant gain-of-function protein. Retinal expression of Pakmyr rescues the R cell connectivity phenotype in dock mutants. These data establish Pak as a critical regulator of axon guidance and a downstream effector of Dock in vivo.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::daafd99e2f9aafda93082c6dd20183bcTest

المؤلفون: Ivan Rodriguez, Peter Mombaerts, Anne Vassalli, Thomas Bozza, Paul Feinstein

المصدر: Cell. (6):833-846

مصطلحات موضوعية: medicine.medical_specialty, Recombinant Fusion Proteins, Green Fluorescent Proteins, Growth Cones, Sensory system, Locus (genetics), Mice, Transgenic, Cell Communication, Biology, Receptors, Odorant, General Biochemistry, Genetics and Molecular Biology, Olfactory Receptor Neurons, Mice, Open Reading Frames, Internal medicine, medicine, Coding region, Animals, Cilia, Receptor, Gene, Alleles, Biochemistry, Genetics and Molecular Biology(all), Gene targeting, Gene Expression Regulation, Developmental, Cell Differentiation, Olfactory Bulb, Olfactory bulb, Cell biology, Luminescent Proteins, Endocrinology, nervous system, Gene Targeting, Mutation, Synapses, Axon guidance, Receptors, Adrenergic, beta-2

الوصف: Odorant receptors (ORs) provide the core determinant of identity for axons of olfactory sensory neurons (OSNs) to coalesce into glomeruli in the olfactory bulb. Here, using gene targeting in mice, we examine how the OR protein determines axonal identity. An OR::GFP fusion protein is present in axons, consistent with a direct function of ORs in axon guidance. When the OR coding region is deleted, we observe OSNs that coexpress other ORs that function in odorant reception and axonal identity. It remains unclear if such coexpression is normally prevented by negative feedback on OR gene choice. A drastic reduction in OR protein level produces axonal coalescence into novel, remote glomeruli. By contrast, chimeric ORs and ORs with minor mutations perturb axon outgrowth. Strikingly, the β2 adrenergic receptor can substitute for an OR in glomerular formation when expressed from an OR locus. Thus, ORs have not evolved a unique function in axon guidance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b64ab7e53373a9cb7606fa37561e3a38Test

المؤلفون: Mu-ming Poo, Xiao-bing Yuan, Ming Jin, Chen-bing Guan, Hua-Tai Xu

المصدر: Cell. (2):385-395

مصطلحات موضوعية: RHOA, genetic structures, Growth Cones, Motility, Nerve Tissue Proteins, DEVBIO, General Biochemistry, Genetics and Molecular Biology, MOLNEURO, Rats, Sprague-Dawley, Cell Movement, Cerebellum, medicine, Extracellular, Animals, Calcium Signaling, Growth cone, Cells, Cultured, Neurons, biology, Biochemistry, Genetics and Molecular Biology(all), Slit, Cell biology, Rats, medicine.anatomical_structure, biology.protein, Intercellular Signaling Peptides and Proteins, Soma, Axon guidance, Calcium, CELLBIO, Neuron, sense organs, rhoA GTP-Binding Protein

الوصف: Neuronal migration and growth-cone extension are both guided by extracellular factors in the developing brain, but whether these two forms of guidance are mechanistically linked is unclear. Application of a Slit-2 gradient in front of the leading process of cultured cerebellar granule cells led to the collapse of the growth cone and the reversal of neuronal migration, an event preceded by a propagating Ca(2+) wave from the growth cone to the soma. The Ca(2+) wave was required for the Slit-2 effect and was sufficient by itself to induce the reversal of migration. The Slit-2-induced reversal of migration required active RhoA, which was accumulated at the front of the migrating neuron, and this polarized RhoA distribution was reversed during the migration reversal induced by either the Slit-2 gradient or the Ca(2+) wave. Thus, long-range Ca(2+) signaling coordinates the Slit-2-induced changes in motility at two distant parts of migrating neurons by regulating RhoA distribution.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24d3e896c1b032ac288c041ed6e9a9d5Test