المؤلفون: Louis-Philippe Croteau, Tzu Jen Kao, Artur Kania

المصدر: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)

مصطلحات موضوعية: 0301 basic medicine, animal structures, Science, Growth Cones, Article, Cell membrane, 03 medical and health sciences, 0302 clinical medicine, Developmental biology, Netrin, medicine, Animals, Ephrin, Axon, Growth cone, Receptor, 030304 developmental biology, Motor Neurons, 0303 health sciences, Multidisciplinary, Axon and dendritic guidance, Chemistry, fungi, Membrane Proteins, Netrin-1, Ephrin-A5, Axons, Axon Guidance, Cell biology, 030104 developmental biology, medicine.anatomical_structure, nervous system, Proteolysis, embryonic structures, Medicine, Axon guidance, Ephrin A5, sense organs, Chickens, 030217 neurology & neurosurgery

الوصف: Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbdcce1d25825d5f520f4497f21fea2fTest
https://doi.org/10.1038/s41598-019-48519-0Test

المؤلفون: Miguel E. Domínguez-Romero, Paula G. Slater

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 8344, p 8344 (2021)
International Journal of Molecular Sciences

مصطلحات موضوعية: 0301 basic medicine, Nervous system, QH301-705.5, medicine.medical_treatment, Growth Cones, Central nervous system, Review, Biology, Catalysis, Inorganic Chemistry, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, guidance cues, Biology (General), Physical and Theoretical Chemistry, Growth cone, QD1-999, Molecular Biology, Spectroscopy, Regeneration (biology), Organic Chemistry, axon regeneration, General Medicine, Axons, spinal cord injury, Axon Guidance, Nerve Regeneration, Computer Science Applications, growth cone, axotomy, Chemistry, Crosstalk (biology), 030104 developmental biology, medicine.anatomical_structure, Peripheral nervous system, Axon guidance, Axotomy, Neuroscience, 030217 neurology & neurosurgery, Signal Transduction

الوصف: During neuronal development and regeneration axons extend a cytoskeletal-rich structure known as the growth cone, which detects and integrates signals to reach its final destination. The guidance cues “signals” bind their receptors, activating signaling cascades that result in the regulation of the growth cone cytoskeleton, defining growth cone advance, pausing, turning, or collapse. Even though much is known about guidance cues and their isolated mechanisms during nervous system development, there is still a gap in the understanding of the crosstalk between them, and about what happens after nervous system injuries. After neuronal injuries in mammals, only axons in the peripheral nervous system are able to regenerate, while the ones from the central nervous system fail to do so. Therefore, untangling the guidance cues mechanisms, as well as their behavior and characterization after axotomy and regeneration, are of special interest for understanding and treating neuronal injuries. In this review, we present findings on growth cone guidance and canonical guidance cues mechanisms, followed by a description and comparison of growth cone pathfinding mechanisms after axotomy, in regenerative and non-regenerative animal models.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b27b1ec1e18b79bf6c4e4824e3977867Test
https://doi.org/10.3390/ijms22158344Test

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: Sijung Yun, Hyungsuk Kim, Tristin Baxter, Whitney S. Livingston, Joseph Fetta, Vincent Mysliwiec, Christiana Martin, Jessica Gill

المصدر: Psychiatry Research. 251:261-265

مصطلحات موضوعية: Adult, Genetic Markers, Male, 0301 basic medicine, Circulating mirnas, Growth Cones, Bioinformatics, behavioral disciplines and activities, Article, Cohort Studies, Stress Disorders, Post-Traumatic, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, mental disorders, microRNA, Humans, Circulating MicroRNA, Wnt Signaling Pathway, Biological Psychiatry, Veterans, Combat Disorders, Sequence Analysis, RNA, Wnt signaling pathway, Peripheral blood, Axon Guidance, Biomarker (cell), Psychiatry and Mental health, Posttraumatic stress, 030104 developmental biology, Cohort, Female, Axon guidance, Psychology, 030217 neurology & neurosurgery, Clinical psychology

الوصف: Posttraumatic stress disorder (PTSD) affects many returning combat veterans, but underlying biological mechanisms remain unclear. In order to compare circulating micro RNA (miRNA) of combat veterans with and without PTSD, peripheral blood from 24 subjects was collected following deployment, and isolated miRNA was sequenced. PTSD was associated with 8 differentially expressed miRNA. Pathway analysis shows that PTSD is related to the axon guidance and Wnt signaling pathways, which work together to support neuronal development through regulation of growth cones. PTSD is associated with miRNAs that regulate biological functions including neuronal activities, suggesting that they play a role in PTSD symptomatology.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::669aeac8947569dbb20d24ea226e1cf4Test
https://doi.org/10.1016/j.psychres.2017.01.081Test

المؤلفون: Kevin M. Patel, Timothy M. Gomez, Patrick C. Kerstein

المصدر: The Journal of Neuroscience. 37:1568-1580

مصطلحات موضوعية: Talin, 0301 basic medicine, animal structures, Growth Cones, Integrin, macromolecular substances, Focal adhesion, Xenopus laevis, 03 medical and health sciences, Cell Adhesion, Animals, Humans, Calcium Signaling, Growth cone, Research Articles, Paxillin, biology, Calpain, General Neuroscience, Axon extension, Axon Guidance, Cell biology, 030104 developmental biology, Spinal Cord, Focal Adhesion Protein-Tyrosine Kinases, embryonic structures, Proteolysis, biology.protein, Axon guidance, biological phenomena, cell phenomena, and immunity, Filopodia

الوصف: Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca2+) is an essential signal for axon guidance that mediates opposing effects on growth cone motility. The diverse effects of Ca2+arise from the precise localization of Ca2+signals into microdomains containing specific Ca2+effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca2+signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain. However, how calpain regulates growth cone motility remains unclear. Here, we identify the adhesion proteins talin and focal adhesion kinase (FAK) as proteolytic targets of calpain inXenopus laevisspinal cord neurons bothin vivoandin vitro. Inhibition of calpain increases the localization of endogenous adhesion signaling to growth cone filopodia. Using live cell microscopy and specific calpain-resistant point-mutants of talin (L432G) and FAK (V744G), we find that calpain inhibits paxillin-based adhesion assembly through cleavage of talin and FAK, and adhesion disassembly through cleavage of FAK. Blocking calpain cleavage of talin and FAK inhibits repulsive turning from focal uncaging of Ca2+within filopodia. In addition, blocking calpain cleavage of talin and FAKin vivopromotes Rohon–Beard peripheral axon extension into the skin. These data demonstrate that filopodial Ca2+signals regulate axon outgrowth and guidance through calpain regulation of adhesion dynamics through specific cleavage of talin and FAK.SIGNIFICANCE STATEMENTThe proper formation of neuronal networks requires accurate guidance of axons and dendrites during development by motile structures known as growth cones. Understanding the intracellular signaling mechanisms that govern growth cone motility will clarify how the nervous system develops and regenerates, and may identify areas of therapeutic intervention in disease or injury. One important signal that controls growth cones is that of local Ca2+transients, which control the rate and direction of axon outgrowth. We demonstrate here that Ca2+-dependent inhibition axon outgrowth and guidance is mediated by calpain proteolysis of the adhesion proteins talin and focal adhesion kinase. Our findings provide mechanistic insight into Ca2+/calpain regulation of growth cone motility and axon guidance during neuronal development.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::25b80a375848666e2076752217b0fdf0Test
https://doi.org/10.1523/jneurosci.2769-16.2016Test

المؤلفون: Edwin A Suarez-Zayas, Timothy M. Gomez, Caitlin A Short

المصدر: Current Opinion in Neurobiology. 39:77-85

مصطلحات موضوعية: Neurons, 0301 basic medicine, Cell type, Neurogenesis, General Neuroscience, Axon extension, Growth Cones, Cell, Biology, Article, Axons, Cell biology, Extracellular matrix, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Cell Movement, Cancer cell, Cell Adhesion, medicine, Humans, Axon guidance, Growth cone, Cell adhesion

الوصف: Axon extension, guidance and tissue invasion share many similarities to normal cell migration and cancer cell metastasis. Proper cell and growth cone migration requires tightly regulated adhesion complex assembly and detachment from the extracellular matrix (ECM). In addition, many cell types actively remodel the ECM using matrix metalloproteases (MMPs) to control tissue invasion and cell dispersal. Targeting and activating MMPs is a tightly regulated process, that when dysregulated, can lead to cancer cell metastasis. Interestingly, new evidence suggests that growth cones express similar cellular and molecular machinery as migrating cells to clutch retrograde actin flow on ECM proteins and target matrix degradation, which may be used to facilitate axon pathfinding through the basal lamina and across tissues.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ec389ec63c6fe00c6aa2cc3ecf1341aTest
https://doi.org/10.1016/j.conb.2016.04.012Test

المؤلفون: Ferdi Ridvan Kiral, Vincent J. Dercksen, Max von Kleist, Steffen Prohaska, Heike Wolfenberg, Mehmet Neset Özel, Josephine Brummer, Marian Moldenhauer, P. Robin Hiesinger, Abhishek Kulkarni, Martin Weiser, Ilsa-Maria Daumann, Amr Hasan

المصدر: Dev Cell

مصطلحات موضوعية: Neurogenesis, Growth Cones, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Live cell imaging, medicine, Synapse formation, Animals, Drosophila Proteins, Computer Simulation, Pseudopodia, Axon, Growth cone, Molecular Biology, Analysis method, 030304 developmental biology, 0303 health sciences, Synapse assembly, GTPase-Activating Proteins, Intracellular Signaling Peptides and Proteins, Gene Expression Regulation, Developmental, Cell Biology, Phosphoproteins, Axons, medicine.anatomical_structure, Entire axon, Drosophila melanogaster, Synapses, Axon guidance, Seeding, Neuroscience, Filopodia, 030217 neurology & neurosurgery, Developmental Biology

الوصف: SummaryFollowing axon pathfinding, growth cones transition from stochastic filopodial exploration to the formation of a limited number of synapses. How the interplay of filopodia and synapse assembly ensures robust connectivity in the brain has remained a challenging problem. Here, we developed a new 4D analysis method for filopodial dynamics and a data-driven computational model of synapse formation for R7 photoreceptor axons in developing Drosophila brains. Our live data support a ‘serial synapse formation’ model, where at any time point only a single ‘synaptogenic’ filopodium suppresses the synaptic competence of other filopodia through competition for synaptic seeding factors. Loss of the synaptic seeding factors Syd-1 and Liprin-α leads to a loss of this suppression, filopodial destabilization and reduced synapse formation, which is sufficient to cause the destabilization of entire axon terminals. Our model provides a filopodial ‘winner-takes-all’ mechanism that ensures the formation of an appropriate number of synapses.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9481c4ec2fa5d1a8f71d158b81352a54Test
https://europepmc.org/articles/PMC6702111Test/

المؤلفون: Jing, Xu, Michael, Xu, YuChia, Wang, R Paige, Mathena, Jieqiong, Wen, Pengbo, Zhang, Orion, Furmanski, C David, Mintz

المصدر: Neurotoxicol Teratol

مصطلحات موضوعية: Rats, Sprague-Dawley, Chlorides, Isoflurane, Anesthetics, Inhalation, Growth Cones, Primary Cell Culture, Animals, Semaphorin-3A, Receptors, GABA-A, Article, Axon Guidance

الوصف: BACKGROUND: General anesthetics (GAs) may exert harmful effects on the developing brain by disrupting neuronal circuit formation. Anesthetics that act on γ-aminobutyric acid (GABA) receptors can interfere with axonal growth cone guidance, a critical process in the assembly of neuronal circuitry. Here we investigate the mechanism by which isoflurane prevents sensing of the repulsive guidance cue, Semaphorin 3A (Sema3A). METHODS: Growth cone sensing was assayed by measuring growth cone collapse in dissociated neocortical cultures exposed to recombinant Sema3A in the presence or absence of isoflurane and/or a panel of reagents with specific actions on components of the GABA receptor and chloride ion systems. RESULTS: Isoflurane exposure prevents Sema3A induced growth cone collapse. A GABA(A) α2 specific agonist replicates this effect (36.83±3.417% vs 70.82±2.941%, in the Sema3A induced control group, p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::2dfecd92679d5bb90e3d4d5d8bbd3f60Test
https://pubmed.ncbi.nlm.nih.gov/31251980Test

المؤلفون: Hiromu Hino, Cory J. Weaver, Tine Verreet, Fabienne E. Poulain, Masahiko Hibi

المصدر: eNeuro

مصطلحات موضوعية: DYNAMICS, genetic structures, Mitochondrion, Animals, Genetically Modified, 0302 clinical medicine, Syntaphilin, axon growth, POSITION, Axon, Zebrafish, 0303 health sciences, CONSTRUCTION, biology, Chemistry, General Neuroscience, General Medicine, New Research, Cell biology, Mitochondria, mitochondria, confocal live imaging, medicine.anatomical_structure, Life Sciences & Biomedicine, Filopodia, EXPRESSION, PROTEINS, Growth Cones, Neuronal Outgrowth, Nerve Tissue Proteins, Development, 03 medical and health sciences, MOTILITY, medicine, Animals, CELL, Growth cone, 030304 developmental biology, Science & Technology, MICROTUBULE, GUIDANCE, Neurosciences, Membrane Proteins, 2.1, biology.organism_classification, zebrafish, TRANSPORT, Axons, Axoplasmic transport, visual system, Axon guidance, Neurosciences & Neurology, sense organs, 030217 neurology & neurosurgery

الوصف: Mitochondria are abundantly detected at the growth cone, the dynamic distal tip of developing axons that directs growth and guidance. It is, however, poorly understood how mitochondrial dynamics relate to growth cone behaviorin vivo, and which mechanisms are responsible for anchoring mitochondria at the growth cone during axon pathfinding. Here, we show that in retinal axons elongating along the optic tract in zebrafish, mitochondria accumulate in the central area of the growth cone and are occasionally observed in filopodia extending from the growth cone periphery. Mitochondrial behavior at the growth conein vivois dynamic, with mitochondrial positioning and anterograde transport strongly correlating with growth cone behavior and axon outgrowth. Using novel zebrafish mutant lines that lack the mitochondrial anchoring proteins Syntaphilin a and b, we further show that Syntaphilins contribute to mitochondrial immobilization at the growth cone. Syntaphilins are, however, not required for proper growth cone morphology and axon growthin vivo, indicating that Syntaphilin-mediated anchoring of mitochondria at the growth cone plays only a minor role in elongating axons.

وصف الملف: Electronic-Print

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91c50819be12f1add3188fc4ea906811Test
https://pubmed.ncbi.nlm.nih.gov/31481398Test

المؤلفون: Yuhan Hu, Annika G. Samuelson, Alexandra Magee, Laura Anne Lowery, Garrett M. Cammarata, Paula G. Slater

المصدر: J Cell Sci

مصطلحات موضوعية: CKAP5, Growth Cones, Xenopus, macromolecular substances, Xenopus Proteins, Biology, Microtubules, Xenopus laevis, 03 medical and health sciences, 0302 clinical medicine, Microtubule, Animals, Cytoskeleton, Growth cone, Actin, 030304 developmental biology, 0303 health sciences, Cell Biology, biology.organism_classification, Ephrin-A5, Actins, Axons, Axon Guidance, Cell biology, Actin Cytoskeleton, Axon guidance, Ephrin A5, Microtubule-Associated Proteins, 030217 neurology & neurosurgery, Research Article

الوصف: It has long been established that neuronal growth cone navigation depends on changes in microtubule (MT) and F-actin architecture downstream of guidance cues. However, the mechanisms by which MTs and F-actin are dually coordinated remain a fundamentally unresolved question. Here, we report that the well-characterized MT polymerase, XMAP215 (also known as CKAP5), plays an important role in mediating MT–F-actin interaction within the growth cone. We demonstrate that XMAP215 regulates MT–F-actin alignment through its N-terminal TOG 1–5 domains. Additionally, we show that XMAP215 directly binds to F-actin in vitro and co-localizes with F-actin in the growth cone periphery. We also find that XMAP215 is required for regulation of growth cone morphology and response to the guidance cue, Ephrin A5. Our findings provide the first strong evidence that XMAP215 coordinates MT and F-actin interaction in vivo. We suggest a model in which XMAP215 regulates MT extension along F-actin bundles into the growth cone periphery and that these interactions may be important to control cytoskeletal dynamics downstream of guidance cues. This article has an associated First Person interview with the first author of the paper.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::481b06ec873007340df32b05c183944fTest
https://doi.org/10.1242/jcs.224311Test