The transcript encoding translationally controlled tumor protein (Tctp), a molecule correlated with aggressive breast cancers, was identified among the most abundant in genome-wide screens of axons, suggesting that Tctp is important in neurons. Here, we tested the role of Tctp in retinal axon development in Xenopus laevis. We report that Tctp deficiency results in stunted and splayed retinotectal projections that fail to innervate the optic tectum at the normal developmental time due to impaired axon extension. Tctp-deficient axons exhibit defects associated with mitochondrial dysfunction and we show that Tctp interacts in the axonal compartment with myeloid cell leukemia 1 (Mcl1), a pro-survival member of the Bcl-2 family. Mcl1 knockdown gives rise to similar axon misprojection phenotypes, and we provide evidence that Tctps anti-apoptotic activity is necessary for the normal development of the retinotectal projection. The findings suggest that Tctp supports the development of the retinotectal ...
Pathogenesis of the autoimmune disease multiple sclerosis (MS) is associated with progressive deterioration of the myelin sheath surrounding neuronal axons; however, axon damage may also contribute to MS-associated neurodegeneration. Nikić et al. used in vivo imaging and electron microscopy to examine axon damage in a mouse model of MS (EAE, experimental autoimmune encephalitis). In EAE mice, swelling in discrete sites on axons was observed, which was then followed by axon fragmentation. In many cases, damaged axons retained myelin; in some cases, axon damage was reversible. Axon damage was preceded by mitochondrial pathology, which was associated with the presence of microglia and the production of reactive oxygen and nitrogen species. Induction of oxidative or nitrosative stress was sufficient to induce mitochondrial pathology and axon damage in normal mice, and their blockade in EAE mice alleviated axon damage. Lesion biopsies from MS patients also showed similar axon (above, right) and ...
TY - JOUR. T1 - Dystroglycan is a scaffold for extracellular axon guidance decisions. AU - Lindenmaier, L. Bailey. AU - Parmentier, Nicolas. AU - Guo, Caiying. AU - Tissir, Fadel. AU - Wright, Kevin. PY - 2019/2/13. Y1 - 2019/2/13. N2 - Axon guidance requires interactions between extracellular signaling molecules and transmembrane receptors, but how appropriate context-dependent decisions are coordinated outside the cell remains unclear. Here we show that the transmembrane glycoprotein Dystroglycan interacts with a changing set of environmental cues that regulate the trajectories of extending axons throughout the mammalian brain and spinal cord. Dystroglycan operates primarily as an extracellular scaffold during axon guidance, as it functions non-cell autonomously and does not require signaling through its intracellular domain. We identify the transmembrane receptor Celsr3/Adgrc3 as a binding partner for Dystroglycan, and show that this interaction is critical for specific axon guidance events ...
Axonal localization of viral membrane proteins promoted by Us9 missense mutants correlates with degree of anterograde spread in the rodent nervous system. Neuro
The eye is a peripheral outpost of the central nervous system (CNS) where the retinal ganglion cells (RGCs) reside. RGC axons navigate to their targets in a remarkably stereotyped and error-free manner and it is this process of directed growth that underlies the complex organization of the adult brain. The RGCs are the only retinal neurons to project into the brain and their peripheral location makes them an unusually accessible population of projection neurons for experiments involving in vivo gene transfer, anatomical tracing, transplantation and in vitro culture. In this paper, we review recent findings that have contributed to our understanding of some of the guidance decisions that axons make in the developing visual system. We look at two choice points in the pathway, the optic nerve head (onh) and the midline chiasm, and discuss evidence that supports the idea that key molecules in guiding axon growth at these junctures are netrin-1 (onh) and ephrin-B (chiasm). In the optic tectum where RGC axon
Proteins characteristic of growing axons often fail to be induced or transported along axons that have been interrupted far from their cell bodies in the adult mammalian CNS. Here, we inquire whether long axons in the mammalian CNS can support efficient axonal transport and deposition of one such protein, GAP-43, when the protein is induced in neuron cell bodies. We have used immunocytochemistry to follow the fate of GAP-43 in dorsal column axons ascending the rat spinal cord from dorsal column axons ascending the rat spinal cord from dorsal root ganglion (DRG) neurons, after synthesis of the protein is induced in these cells by peripheral nerve injury. Sciatic nerve lesions do lead to an accumulation of GAP-43 in dorsal column axons derived from the lumbar DRG. However, in distal segments of these CNS axons, accumulation of GAP-43 is apparent only after a delay of 1-2 weeks, in contrast to its rapid accumulation in axon segments within the PNS environment, suggesting that deposition and ...
zag-1 activity establishes several neuronal characteristics, such as cell position, axonal structure and gene-expression profile. Although zag-1 mutations confer various defects on sensory, motor and interneurons, common or related phenotypes are evident. These include the absence of stereotypic axon branches and upregulation of neurotransmitter biosynthetic and reuptake genes. zag-1 functions less to define neuron identity per se and more to generate features characteristic of a particular type of neuron. The specificity and selectivity of zag-1 phenotypes for each neuron type suggests that zag-1 acts in combination with other cell-type-specific factors to control differentiation.. SRA-6 is a candidate chemosensory receptor, based on its predicted seven transmembrane domain topology and expression in amphid sensory neurons ASH and ASI (Troemel et al., 1995). sra-6::gfp provides an ideal indicator of PVQ development and differentiation, although sra-6 function in interneuron PVQ is unclear. ...
This is a message to people interested (or potentially interested) in the development of the Drosophila motor axon system and CNS: I recently constructed a World Wide Web site (linked to our homepage, which is http://www.caltech.edu/~zinn/ ) on motor axon development in flies. This consists at present of a gallery of high-resolution Photoshop images (,35 images of antibody-stained embryos photographed with DIC optics, and several diagrams) of the neuromuscular system in embryos, with accompanying text. Most of the images in the current version are of wild-type embryos stained with the 1D4 antibody against Fasciclin II, which specifically labels motor axons (Van Vactor et al., Cell 73, 1137-1153 (1993)). The same segments are shown in several focal planes, so that the viewer can see the details of the pathways as if they were examining an actual embryo under the microscope. There are also embryos double-stained for PNS, muscle, and tracheal markers, so that motor axon development can be keyed to ...
In contrast to peripheral nerves, damaged axons of the mammalian brain and spinal cord rarely regenerate. Although the nature of the neuronal environment, particularly inhibitory molecules on myelin and in glial scar tissue, can partially explain the lack of regeneration in the CNS, intrinsic neuronal factors also have an influence. Intrinsic influences on axon growth are neuronal age (Lagunowich et al., 1992; Li et al., 1995), neuronal cell type (Benfey et al., 1985; Rossi et al., 2001), distance of axotomy from the cell body (Fernandes et al., 1999), and conditioning (McQuarrie, 1978; Neumann and Woolf, 1999). Thus, embryonic axons grow through environments that ordinarily block regeneration, some axons mount a vigorous regenerative response whereas some never regenerate, axons cut close to the cell body show a greater regenerative response than those cut more distally, and axons may regenerate with greater vigor if they have been damaged some days previously.. For successful regeneration, the ...
One of the most challenging problems in biology is to understand how the billions of neurons in the mammalian nervous system wire up to form functional neural circuits that underlie all behaviour. This has been one of the most intensely studied areas of developmental neurobiology in the past, and a number of important proteins have been identified that instruct axons to project to their specific target regions (so called axon guidance proteins).. Our current work focuses on how axon guidance proteins are detected by receptor proteins on growing axons, how these receptors signal and how they are regulated by for example endocytosis or proteolytic cleavage. Remarkably, our nervous system contains billions of connections but no more than a hundred axon guidance proteins. How can this relatively small number of proteins set up the wiring of a disproportionally large number of connections with many different characteristics such as trajectories or synaptic partners? Evidence is emerging that the ...
Neocortical interneurons display great morphological and physiological variability and are ideally positioned to control circuit dynamics, although their exact role is still poorly understood. To better understand this diversity, we have performed a detailed anatomical and physiological characterization of 3 subtypes of visual cortex interneurons, isolated from transgenic mice which express green fluorescent protein in somatostatin, parvalburnin, and neuropeptide Y positive neurons. We find that these 3 groups of interneurons have systematic differences in dendritic and axonal morphologies and also characteristically differ in the frequencies, amplitude, and kinetics of the spontaneous excitatory and inhibitory synaptic currents they receive. Moreover, we detect a correlation between the kinetics of their synaptic inputs and quantitative aspects of their axonal arborizations. This suggests that different interneuron types could channel different temporal patterns of activity. Our results also ...
Nakamura, T., et al. (2017). Novel role of Rac-Mid1 signaling in medial cerebellar development. Development 144(10): 1863-1875. PubMed ID: 28512198 Nakaya, Y., Kuroda, S., Katagiri, Y. T., Kaibuchi, K. and Takahashi Y. (2004). Mesenchymal-epithelial transition during somitic segmentation is regulated by differential roles of Cdc42 and Rac1. Dev Cell. 7(3): 425-38. 15363416 Newsome, T. P., Schmidt, S., Dietzl, G., Keleman, K., Asling, B., Debant, A., and Dickson, B. J. (2000). Trio combines with Dock to regulate Pak activity during photoreceptor axon pathfinding in Drosophila. Cell 101: 283-94. PubMed Citation: 10847683 Ng, J., et al. (2002). Rac GTPases control axon growth, guidance and branching. Nature 416: 442-447. 11919635 Ng, J. and Luo, L. (2004). Rho GTPases regulate axon growth through convergent and divergent signaling pathways. Neuron 44: 779-793. 15572110 Ng, J. (2008). TGF-β signals regulate axonal development through distinct Smad-independent mechanisms. Development 135(24): ...
Dive into the research topics of A global pathway selection algorithm for the reduction of detailed chemical kinetic mechanisms. Together they form a unique fingerprint. ...
The AKT-GSK3β-eIF2Bε signaling module plays a key role in promoting axon regeneration in the adult mammalian central nervous system.
While commissural axons pathways are absent in comm mutants, other aspects of CNS development appear normal, including formation of longitudinal axon pathways, nerve roots, peripheral axon pathways, and peripheral sensory neurons. The mutant phenotype appears to be quite specific to the midline of the CNS, since the pattern for cuticle, segmentation, and muscles are normal. The normal axon projection of the ventral unpaired medial neurons (VUMs) is particularly interesting because the VUM cell bodies are located at the midline and extend growth cones that bifurcate and project away from the midline and toward the intersegmental nerve root. The fact that this happens in a relatively normal fashion in comm mutants suggests that there is no physical barrier preventing growth cones from extending near the midline. Later in embryogenesis, in the absence of commissural axon pathways and their surrounding nonneuronal cells holding the two sides of the CNS together, the CNS starts to unzip as it splits ...
Data Availability StatementNot applicable Abstract Several neuronal guidance proteins, known as semaphorin molecules, function in the immune system. not been determined yet if such discrepancy between the in vitro and in vivo results can FAM162A be explained, in part, by a different receptor or a particular combination of receptors involved in Sema4As actions in different tissues and organs. The presence and signaling of distinct Sema4A receptors on different immune cells in vivo can also influence the outcome of its action in the immune response to Ag. For some time, it was believed that the only functional receptor for Sema4A on T cells was Tim-2 (Kumanogoh et al., 2002a). However, a more recent study has shown that Sema4A is functionally engaged with NRP-1 on Treg cells; this engagement is necessary for Treg cell stability and function at the sites of inflammation (Delgoffe et al., 2013) (Fig. ?(Fig.3).3). We and others have shown that DC express Sema4A receptors Plexins B1, B2, and D1 (Smith ...
Developing motoneurons in zebrafish embryos follow a stereotyped sequence of axonal outgrowth and accurately project their axons to cell-specific target muscles. During axonal pathfinding, an identified motoneuron pioneers the peripheral motor pathway. Growth cones of later motoneurons interact with the pioneer via contact, coupling, and axonal fasciculation. In spite of these interactions, ablation of the pioneer motoneuron does not affect the ability of other identified motoneurons to select the pathways that lead to appropriate target muscles. We conclude that interactions between these cells during pathfinding are not required for accurate pathway selection ...
Precise spatiotemporal control of axon guidance factor expression is a prerequisite for formation of functional neuronal connections. Although Netrin/Dcc- and Robo/Slit-mediated attractive and repulsive guidance of commissural axons have been extensively studied, little is known about mechanisms controlling mediolateral positioning of longitudinal axons in vertebrates. Here, we use a genetic approach in zebrafish embryos to study pathfinding mechanisms of dopaminergic and neuroendocrine longitudinal axons projecting from the hypothalamus into hindbrain and spinal cord. The transcription factors Sim1a and Arnt2 contribute to differentiation of a defined population of dopaminergic and neuroendocrine neurons. We show that both factors also control aspects of axon guidance: Sim1a or Arnt2 depletion results in displacement of hypothalamo-spinal longitudinal axons towards the midline. This phenotype is suppressed in robo3 guidance receptor mutant embryos. In the absence of Sim1a and Arnt2, expression ...
This study will use two-photon cellular imaging in an animal model of human multiple sclerosis (MS) to determine how neural-immune interactions may damage the nerve cells communication cables (axons) to produce disabling cognitive and motor disabilities. MS afflicts about 400,000 people in this country. It is an autoimmune disease in which the bodys immune cells mistake as foreign and attack some tissues in the brain and especially in the spinal cord (central nervous system, CNS). MS specifically targets a nerve cells axon and the myelin sheath that covers it. Axons carry nerve cell messages from one cell to another. Just how immune cells inflict damage to axons, however, is not yet known. The investigators hypothesize that innate immune cells, the bodys first line of defense, ordinarily help maintain the equilibrium of axons. But in autoimmune inflammation, they turn deadly and fatally injure axons. Since it is not currently feasible to image nerve-immune cell interactions in MS ...
This study will use two-photon cellular imaging in an animal model of human multiple sclerosis (MS) to determine how neural-immune interactions may damage the nerve cells communication cables (axons) to produce disabling cognitive and motor disabilities. MS afflicts about 400,000 people in this country. It is an autoimmune disease in which the bodys immune cells mistake as foreign and attack some tissues in the brain and especially in the spinal cord (central nervous system, CNS). MS specifically targets a nerve cells axon and the myelin sheath that covers it. Axons carry nerve cell messages from one cell to another. Just how immune cells inflict damage to axons, however, is not yet known. The investigators hypothesize that innate immune cells, the bodys first line of defense, ordinarily help maintain the equilibrium of axons. But in autoimmune inflammation, they turn deadly and fatally injure axons. Since it is not currently feasible to image nerve-immune cell interactions in MS ...
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Nervous system-specific eve mutants were created by removing regulatory elements from a 16 kb transgene capable of complete rescue of normal eve function. When transgenes lacking the regulatory element for either RP2+a/pCC, EL or U/CQ neurons were placed in an eve-null background, eve expression was completely eliminated in the corresponding neurons, without affecting other aspects of eve expression. Many of these transgenic flies were able to survive to fertile adulthood. In the RP2+a/pCC mutant flies: (1) both RP2 and aCC showed abnormal axonal projection patterns, failing to innervate their normal target muscles; (2) the cell bodies of these neurons were positioned abnormally; and (3) in contrast to the wild type, pCC axons often crossed the midline. The Eve HD alone was able to provide a weak, partial rescue of the mutant phenotype, while both the Groucho-dependent and -independent repressor domains contributed equally to full rescue of each aspect of the mutant phenotype. Complete rescue ...
They are caused by gene mutations that happen in abnormalities in the synthesis or catabolism of proteins, carbohydrates, or fats. The DRG contain pseudounipolar sensory neurons В- so called because they furnish arise to a individual axon that bifurcates, with one involvement projecting to the boundary and the other projecting to the dorsal horn of the spinal cord. Carrots check beta-carotene and former carotenoids cheap 0.18mg alesse with mastercard birth control lawsuit. Furthermore, uncountable of the ocular tissues and fluids collected in bioanalytical studies are present in such low amount or substance that reanalysis may be unaccommodating or unachievable, depending on the assay approach utilized. A Ladd returns is performed, during which the intestine is straightened out and bands contributing to the misalignment are divided. Heart disease and the incendiary activity dapoxetine 30mg online erectile dysfunction medication non prescription. The use of such instruments to right off the bat ...
Neurons are polarized cells with axons (the site of signal output) and dendrites (the sites of signal input). Not only are these functionally different parts of the cell, but the morphology of axons and dendrites is very different as well. Two groups report that glycogen synthase kinase 3β (GSK-3β) is at the center of a process that regulates the balance of axons and dendrites. Jiang et al. and Yoshimura et al. reported that when GSK-3β activity was increased by transfection of isolated embryonic hippocampal neurons with a constitutively active mutant, the number of cells that formed an axon or extended neurite was decreased, and when GSK-3β activity was inhibited, using multiple methods, the number of cells producing multiple axons increased. The overall number of neurites was unchanged. Inhibition of GSK-3β activity in cultured neurons before or after polarity had been established produced an increase in the number of cells with multiple axons, suggesting a role for GSK-3β in both ...
Its not as rear as you make it out. Its quite common in SMA and SBMA and some muscular disorders to fasciculate well in advance of weakness or EMG changes. Ive know people that Ive talked with that twitched in their teens only later to be diagnosed with ALS, in-approrpriately, then diagnosis changed to another MND 30 years later. I may be one of them. Ive yet to show changes but Ive been told even after 20 years, Im not out of woods. Not by Dr. Google...or vet....etc. Ive had every test you can imagine, all negative, but still Im a very interesting subject because I fasciculate and have an elevated CPK for 20+ years. Nothing sinister on EMG. But I still see a neurologist. They want to run tests that my insurance company wont pay for....I wont do it unless my Son or Daughter show changes...Lately, my son started to fasciculate and his hands and feet are cramping..might be time to do more tests ...
Yuanyuan (Kevin) Liu has been awarded an American Heart Association Predoctoral Fellowship for his research. Yuanyuan is a graduate student in Biological Sciences in Professor Ben Szaros lab. The funding is for 2 years with a $20,000/yr stipend. The title of his award is: Studies of an RNA binding protein and its mRNA targets during central nervous system axon regeneration. Of 115 proposals received, Yuanyuans was among the top 6 percent. More specific details about Yuanyuans study may be found below. After a stroke, patients frequently recover only partially due to the disruption of connections between neurons. In the human brain, axons which mediate these connections, generally fail to regenerate beyond the lesion site. In contrast, injured central nervous system neurons in lower vertebrates, such as the frog, can often fully regenerate. Yuanyuan Liu is using the regenerating optic nerve of the frog Xenopus laevis as a model system to study the mechanisms of successful central nervous ...
Nitric oxide gets neurons together. And it seems to do it backward. Work by Nikonenko et al. suggests that a protein called PSD-95 prompts nitric oxide release from postsynaptic dendritic spines, prompting nearby presynaptic ...
Hi there, Currently, when I use maven to build the project I have this problem. I have 2 projects: desk_post and desk_post_test (required desk_post) When I run for desk_post -> mvn clean install -> successful -> created: desk_post-1.00.08.00-SNAPSHOT.iar -> the resources folder alread...
Cell surface receptor that plays a functionally redundant role in the inhibition of neurite outgrowth mediated by MAG (By similarity). Plays a functionally redundant role in postnatal brain development. Contributes to normal axon migration across the brain midline and normal formation of the corpus callosum. Does not seem to play a significant role in regulating axon regeneration in the adult central nervous system. Protects motoneurons against apoptosis; protection against apoptosis is probably mediated by MAG (By similarity). Like other family members, plays a role in restricting the number dendritic spines and the number of synapses that are formed during brain development (PubMed:22325200). Signaling mediates activation of Rho and downstream reorganization of the actin cytoskeleton (PubMed:22325200).
SCOTTSDALE, Ariz., Dec. 1, 2016 /PRNewswire/ -- New Axon Signal Magazine Connects TASER Smart Weapons To Wearable Cameras. The Signal Performance Power...
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New research sheds light on the molecular mechanisms underlying axon g...A group led by Michael Hengartner from the University of Zurich in Sw...Hengartner and colleagues then show that UNC-69 physically interacts w...It is known that UNC-76 binds to molecular motor proteins called kin...The short coiled-coil domain-containing protein UNC-69 cooperates with...,Newly,identified,protein,complex,sheds,light,on,axon,growth,mechanism,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
New research sheds light on the molecular mechanisms underlying axon g...A group led by Michael Hengartner from the University of Zurich in Sw...Hengartner and colleagues then show that UNC-69 physically interacts w...It is known that UNC-76 binds to molecular motor proteins called kin......,Newly,identified,protein,complex,sheds,light,on,axon,growth,mechanism,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
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The computational model of in vivo sharp-wave ripples with place cell replay. Excitatory post-synaptic potentials at dendrites gate antidromic spikes arriving from the axonal collateral, and thus determine when the soma and the main axon fire. The model allows synchronous replay of pyramidal cells during sharp-wave ripple event, and the replay is possible in both forward and reverse directions ...
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Principal Investigator:MASU Masayuki, Project Period (FY):2010-04-01 - 2015-03-31, Research Category:Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Project Area:Neural Diversity and Neocortical Organization
The cerebral cortex is essential for all sorts of processing of sense data and motor control. It is where the reasoning and cognition specific to humans (and, to a lesser degree, some other animals) takes place, and is the seat of planning and language, volitional behavior and conscious perceptions, thinking and memory. It is the command center where input sensory information is translated into output motor control. In evolutionary terms, it is the most recently developed part of our brains and has taken over or added to function of older structures.. Its unique and fairly uniform structure (sometimes termed canonical) allows for great plasticity in functioning. It consists of layers1)Six, in the striate cortex.. of gray matter (neuron cells, dendrites and synapses) on the outside (distally) and white matter (axons) beneath, although the difference in colors is less pronounced than those terms may imply. It consists of two lateral hemispheres joined by a bundle of axonal connections, the ...
There is accumulating evidence that RelA is crucial for axon formation during embryonic neural development (Gavaldà et al., 2009). In cervical superficial ganglia, enhanced site-specific Ser536 phosphorylation of RelA in the presence of p50 impairs increases in neurite length and complexity (Gutierrez et al., 2008), whereas RelA suppression by overexpression of either p50 or a dominant-negative IκBα super-repressor in newborn hippocampal neurons results in complete growth arrest (Imielski et al., 2012). It has been suggested that modification of both IκBα and activated RelA determines a functional switch from growth inhibition to growth promotion (Gavaldà et al., 2009; Gutierrez et al., 2008). Moreover, as recently exemplified for hippocampal neurogenesis, the balance between transactivation-competent and -incompetent NF-κB subunits might also be crucial for axogenesis (Imielski et al., 2012). However, such previous experiments were based on in vitro analysis of premature PNS and newborn ...
Netrins. The discovery of netrins came as the remarkable convergence of the search for a chemoattractant for vertebrate commissural axons (3, 4), and the analysis of genes required for circumferential axon guidance inCaenorhabditis elegans (5, 6). Across more than 600 million years of evolution, netrins have retained the function of attracting axons ventrally toward the midline (7). Netrins can also repel some axons, and this function too has been conserved. This was initially inferred from defects in dorsal as well as ventral guidance inunc-6/netrin mutant worms (5), and subsequently confirmed by the direct demonstration of netrins repulsive activity in vertebrates (8) and in flies (9,10).. Identification of the netrin receptors followed from the characterization of two other worm mutants with defects in circumferential guidance: unc-40, which primarily disrupts ventral guidance; and unc-5, which affects only dorsal guidance (5). Both unc-40 and unc-5encode conserved transmembrane proteins ...
The extracellular cue UNC-6/Netrin is a well-known axon guidance molecule and recently it has also been shown to be involved with localization of pre-synaptic complexes. Working through the UNC-40/DCC/Fra receptor, UNC-6/Netrin promotes the formation of pre-synaptic terminals between the pre-synapti …
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The purification of axonal membranes of crustaceans was followed by measuring enrichment in [3H]tetrodotoxin binding capacity and in Na+, K+-ATPase activity. A characteristic of these membranes is their high content of lipids and their low content of protein as compared to other types of plasmatic m …
GO:0048846. The long distance growth of a single cell process, that is involved in the migration of an axon growth cone, where the migration is directed to a specific target site by a combination of attractive and repulsive cues. ...
Slit1 triggers Netrin-1 repulsion for hippocampal neurons on PLL-coated substrate. (A) Last brighfield images of typical growing axons on PLL-coated microwells.
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REGULATION OF AXONAL DEVELOPMENT BY THE cGMP SIGNALING PATHWAY By Zhen Zhao A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirement for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2009 Copyright 2009 Zhen Zhao ii Acknowledgements I would like to express my gratitude to all those who assisted me to complete my work and this thesis. I want to thank University of Southern California, Neuroscience Graduate Program and Zilkha Neurogenic Institute for giving me the opportunity to pursue my doctoral degree. I am deeply indebted to my supervisor Prof. Dr. Le Ma. It was his guidance, encouragement, suggestions and full support that made this work possible. I also have to thank my committee members, Dr. Samantha Buttler, Dr. James Knowles, Dr. Emily Liman, Dr. David Mckemy, Dr. Zuo-zhong Wang and Dr. Qilong Ying for their valuable help, and Dr. Li Zhangs lab, Dr. Jonah Chan and Dr, Zuo-zhong Wangs lab for ...
REGULATION OF AXONAL DEVELOPMENT BY THE cGMP SIGNALING PATHWAY By Zhen Zhao A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirement for the Degree DOCTOR OF PHILOSOPHY (NEUROSCIENCE) December 2009 Copyright 2009 Zhen Zhao ii Acknowledgements I would like to express my gratitude to all those who assisted me to complete my work and this thesis. I want to thank University of Southern California, Neuroscience Graduate Program and Zilkha Neurogenic Institute for giving me the opportunity to pursue my doctoral degree. I am deeply indebted to my supervisor Prof. Dr. Le Ma. It was his guidance, encouragement, suggestions and full support that made this work possible. I also have to thank my committee members, Dr. Samantha Buttler, Dr. James Knowles, Dr. Emily Liman, Dr. David Mckemy, Dr. Zuo-zhong Wang and Dr. Qilong Ying for their valuable help, and Dr. Li Zhangs lab, Dr. Jonah Chan and Dr, Zuo-zhong Wangs lab for ...
TY - JOUR. T1 - B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS. AU - ODonovan, Kevin J.. AU - Ma, Kaijie. AU - Guo, Hengchang. AU - Wang, Chen. AU - Sun, Fang. AU - Han, Seung Baek. AU - Kim, Hyukmin. AU - Wong, Jamie K.. AU - Charron, Jean. AU - Zou, Hongyan. AU - Son, Young Jin. AU - He, Zhigang. AU - Zhong, Jian. N1 - Copyright: Copyright 2014 Elsevier B.V., All rights reserved.. PY - 2014/5. Y1 - 2014/5. N2 - Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as ...
Immature motoneurons are highly susceptible to degeneration following axon injury. The response of perineuronal glia to axon injury may significantly influence neuronal survival and axon regeneration. We have examined the central reactions to neonatal facial nerve transection with emphasis on the expression of complement component C3 (C3) and the multifunctional apolipoprotein J (ApoJ). Axotomy was performed on one-day-old rats. Animals were perfused from eight hours to two weeks after the lesion. The astroglial marker, glial fibrillary acidic protein (GFAP) was increased from one day and the microglial marker OX-42 from two days after injury. ApoJ immunoreactivity was increased in axotomized neuronal perikarya and astroglial cells from one day postaxotomy, but no C3 immunoreactive profiles were found at any postoperative survival time. Cell proliferation as judged by bromodeoxyuridine labeling and immunoreactivity for the cyclin Ki-67 antigen (antibody MIB5) occurred only at two days after ...
TY - JOUR. T1 - Overexpression of ATF3 or the combination of ATF3, c-Jun, STAT3 and Smad1 promotes regeneration of the central axon branch of sensory neurons but without synergistic effects. AU - Fagoe, Nitish D. AU - Attwell, Callan L. AU - Kouwenhoven, Dorette. AU - Verhaagen, J.. AU - Mason, M.R.J.. N1 - © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected] PY - 2015/12/1. Y1 - 2015/12/1. N2 - Peripheral nerve injury results in the activation of a number of transcription factors (TFs) in injured neurons, some of which may be key regulators of the regeneration-associated gene (RAG) programme. Among known RAG TFs, ATF3, Smad1, STAT3 and c-Jun have all been linked to successful axonal regeneration and have known functional and physical interactions. We hypothesised that TF expression would promote regeneration of the central axon branch of DRG neurons in the absence of a peripheral nerve lesion and that ...
The development of the adult visual system of Drosophila requires the establishment of precise retinotopic connections between retinal photoreceptor cell axons and their synaptic partners in the optic lobe of the brain. To assess the role of axon-axon interactions in retinal axon guidance, we used genetic methods to disrupt the normal spatiotemporal order of retinal axon ingrowth. We examined retinal axon projections to the developing first optic ganglion, the lamina, in two mutants in which reduced numbers of ommatidia develop in the eye imaginal disk. We find that in the developing lamina of these mutants, sine oculis and Ellipse, retinal axons project to proper dorsoventral positions despite the absence of the usual array of neighboring retinal axons. In a second approach, we examined animals that were somatic mosaics for the mutation, glass. In glass- animals, retinal axons project aberrantly and the larval optic nerve is absent. We find that in the developing lamina of glass mosaic animals, wild
Antibodies for proteins involved in fasciculation of sensory neuron axon pathways, according to their Panther/Gene Ontology Classification
Oligodendrocyte-derived myelin retards the ability of CNS axons to regenerate following transection. The intrinsic response of CNS axons to an axotomy insult may be vastly different in the absence of myelin. However, the paucity of adequate experimental models has limited detailed investigation of cellular behaviour following axon transection in an unmyelinated CNS environment. In this study we perform laser-induced axotomy of the porcine retinal ganglion cell axon, a physiologically unmyelinated, mature CNS axon that is structurally similar to humans to infer knowledge about axonal behaviour in the absence of myelin. Axotomy-induced changes to the neuronal cytoskeleton and supporting astrocytes during the early stages after transection are delineated by examining the sequence of neurofilament subunit, microtubule (TUB), microtubule associated protein (MAP), glial fibrillary acidic protein (GFAP) and terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL) modification. ...
In contrast to the central nervous system (CNS) nerve fibers do regenerate in the peripheral nervous system (PNS) although in a clinically unsatisfying manner. A major problem is excessive sprouting of regenerating axons which results in aberrant reinnervation of target tissue and impaired functional recovery. In the CNS, the reticulon protein Nogo-A has been identified as a prominent oligodendrocyte expressed inhibitor of long-distance growth of regenerating axons. We show here that the related isoform Nogo-B is abundantly expressed in Schwann cells in the PNS. Other than Nogo-A in oligodendrocytes, Nogo-B does not localize to the myelin sheath but is detected in the ER and the plasma membrane of Schwann cells. Adult sensory neurons that are cultured on nogo-a/b deficient Schwann cells form significantly fewer axonal branches versus those on wildtype Schwann cells, while their maximal axonal extension is unaffected. We demonstrate that this effect of Nogo-B on neuronal morphology is restricted to
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Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP3) receptors and calcium entry through transientreceptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest ...
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We recently noted, in performing a metabolic characterization of mice deleted for LKB1 in the endocrine pancreas and a restricted set of CNS neurons using a RIP2-Cre transgene (Sun et al., 2010b), that older animals became paralyzed. The principal aim of the present study was thus to dissect the pathology behind this change and, in doing so, to determine the role of LKB1 in regulating neuronal polarity and survival in the CNS in vivo.. Although mice null for LKB1 throughout the body die before E11.5, the use of an Emx1-Cre deleter strain to allow deletion in pyramidal neuron progenitors demonstrated that LKB1 is required for the polarization of cultured neurons from the neonatal hippocampus and cortex (Barnes et al., 2007; Shelly et al., 2007). We therefore reasoned that LKB1 might play a similar role in axon development and, importantly, in signal transmission along the spinal cord. Given the crucial role of the spinal cord for the normal control of motor function, we further reasoned that ...
This allowed us to systematically investigate how metabolic cost depends on factors such as axonal geometry and ion channel densities. E.g comparing myelinated and unmyelinated axons with the same axon diameter of 1µm (fibre diameter including myelin sheath was 3.7 µm) we find the following: single APs at a myelinated axons Node of Ranvier have a metabolic cost of 3.5 pmol/cm² ATP per unit membrane area. This is approximately 7 times the amount per AP in hippocampal mossy fibre (0.53 pmol/cm2;[2]) but less than leaky squid axons (5 pmol/cm2). However, Node of Ranvier cover only 0.33% in our myelinated axon. The internodal regions contain hardly any Na+ channels, but a low density of K+ channels (3 µm-2) along internodes, and higher densities at the paranode (80 µm-2). We estimate overall energy consumption based on Na currents at the Node and K along a segment comprising half the internodal fibre on both sides of a node. This yields an AP cost per myelinated axon segment of 0.05 pmol/cm2 ...
Despite the widespread occurrence of axon and synaptic loss in the injured and diseased nervous system, the cellular and molecular mechanisms of these key degenerative processes remain incompletely understood. Wallerian degeneration (WD) is a tightly regulated form of axon loss after injury, which has been intensively studied in large myelinated fibre tracts of the spinal cord, optic nerve and peripheral nervous system (PNS). Fewer studies, however, have focused on WD in the complex neuronal circuits of the mammalian brain, and these were mainly based on conventional endpoint histological methods. Post-mortem analysis, however, cannot capture the exact sequence of events nor can it evaluate the influence of elaborated arborisation and synaptic architecture on the degeneration process, due to the non-synchronous and variable nature of WD across individual axons. To gain a comprehensive picture of the spatiotemporal dynamics and synaptic mechanisms of WD in the nervous system, we identify the factors that
The precision with which neurons form connections is crucial for the normal development and function of thenervous 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 theirappropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understandhow this process is regulated, the complete repertoire of molecular mechanisms that govern the growth conecytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calciumsignals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements ofthe growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal iscritical for growth cone motility but also the source of calcium mobilisation. We provide an example of this ideaby demonstrating that manipulation of ...
Histology in DAI. A number of histological techniques are available to appreciate sequential pathological changes in axons in diffuse axonal injury. These are primarily aimed at shortening the duration at which the axonal changes are seen and to put them in context to various traumatic and non traumatic conditions so as to differentiate the causative mechanism. Axonal swellings or retraction balls, representing transected axons, are the histological hallmark of axonal injury but are usually not visible before 24 to 36 hours by routine H & E staining or with a myelin stain like Luxol fast blue [2]. Silver staining method can reliably demonstrate axonal swellings within 12 to 18 hours [27]. The method has been found to be more sensitive and reliable as compare to H & E staining. However diffuse staining of axons by silver stains may occasionally make differentiation of injured and irregular axons difficult thereby limiting their practical utility [28]. Injuries to the axons may be detected even ...
Authors: Carter, Deborah A. , Lisney, S.J.W. Article Type: Research Article Abstract: Counts of myelinated and unmyelinated axon profiles have been made from normal, uninjured rat sural nerves and from nerves injured 6 months earlier in one of two ways. In one group of rats the nerve was simply cut and left to regenerate, leading to the development of a neuroma in continuity, while in the second group the nerve was cut but then ligated as well to prevent regeneration; this led to stump neuroma formation. After nerve transection and regeneration, with subsequent formation of a neuroma in continuity, there was no change in the number of myelinated axon profiles found 25 …mm proximal to the old injury site when compared with control, but there was an 18% reduction (P , 0.05) in the number of unmyelinated axon profiles. Immediately proximal to the injury site the picture was similar, with there still being the same number of myelinated axon profiles as in control material but here the reduction in ...
Kevin Park, Ph.D. Assistant Professor, Department of Neurological Surgery / The Miami Project, recently published a manuscript in Cell Reports titled Enhanced Transcriptional Activity and Mitochondrial Localization of STAT3 Co-induce Axon Regrowth in Adult Central Nervous System. In this study, Dr. Park and colleagues examined how a classical transcription factor, known as STAT3 locates to different cellular regions and promotes axon regeneration in the inured central nervous system (CNS). Overall, their data provided mechanistic insights into the mode of actions of STAT3 in mature CNS, and demonstrate that capitalizing STAT3s effects in combination with modulation of other growth regulating molecules allows a neural intervention for extensive axon regrowth.. Promoting injured axons to regenerate long distances remains a major challenge, but if effectively attained, could help restore motor and sensory functions that are lost after traumatic injury or in neurodegenerative conditions, said Dr. ...
Many guidance receptors are proteolytically cleaved by membrane-associated metalloproteases of the ADAM family, leading to the shedding of their ectodomains. Ectodomain shedding is crucial for receptor signaling and function, but how this process is controlled in neurons remains poorly understood. Here, we show that the transmembrane protein Lrig2 negatively regulates ... read more ADAM-mediated guidance receptor proteolysis in neurons. Lrig2 binds Neogenin, a receptor for repulsive guidance molecules (RGMs), and prevents premature Neogenin shedding by ADAM17 (TACE). RGMa reduces Lrig2-Neogenin interactions, providing ADAM17 access to Neogenin and allowing this protease to induce ectodomain shedding. Regulation of ADAM17-mediated Neogenin cleavage by Lrig2 is required for neurite growth inhibition by RGMa in vitro and for cortical neuron migration in vivo. Furthermore, knockdown of Lrig2 significantly improves CNS axon regeneration. Together, our data identify a unique ligand-gated mechanism to ...
However, new insights into the basic properties of fast axonal transport are beginning to illuminate the roles that it may play during axonal growth. Although fast axonal transport is often used to refer solely to the movement of materials at the fastest orthograde rate, there is good reason for including in fast axonal transport the translocation of membranous organelles of all types in both directions (Lasek and Brady, 1982). The original descriptions of fast axonal transport (for example, see Lasek, 1967; Dahlstrom and Haggendahl, 1967; Grafstein, 1967) focused on the fastest moving elements leaving the cell bodies and defined this as fast axonal transport. I I FIGURE 3. Various responses of the facial nerve cell bodies following different types of axonal injuries in different animal species. , 1982). Biochemical changes in the nerve cell body occur after the injection of botulinum toxin into the area of neuromuscular junction. Watson (1974) suggested that since botulinum toxin causes a block ...
During development, the axons of retinal ganglion cell (RGC) neurons must decide whether to cross or avoid the midline at the optic chiasm to project to targets on both sides of the brain. By combining genetic analyses with in vitro assays, we show that neuropilin 1 (NRP1) promotes contralateral RGC projection in mammals. Unexpectedly, the NRP1 ligand involved is not an axon guidance cue of the class 3 semaphorin family, but VEGF164, the neuropilin-binding isoform of the classical vascular growth factor VEGF-A. VEGF164 is expressed at the chiasm midline and is required for normal contralateral growth in vivo. In outgrowth and growth cone turning assays, VEGF164 acts directly on NRP1-expressing contralateral RGCs to provide growth-promoting and chemoattractive signals. These findings have identified a permissive midline signal for axons at the chiasm midline and provide in vivo evidence that VEGF-A is an essential axon guidance cue.
Individual neurons in vertebrates are typically highly branched with a complex morphology of their processes (axons and dendrites). In C. elegans almost all neuronal processes are unbranched and extend in a stereotpical fashion. The example in Figure 3 shows a pair of sensory neurons (ASH) with cell bodies located in head ganglia. The two ASH neurons are chemosensory neurons. A single process, the dendrite, extends from the cell body towards the tip of the nose. A second process, the axon, grows first towards the ventral cord through the amphid commissure. It then turns anteriorly and loops in a halfcircle around the pharynx (not visible) within a large axon bundle - the nerve ring (note: the processes in the ventral cord in the figure belong to a second pair of neurons (PVQ) with cell bodies in the tail). The nerve ring is a horseshoe-shaped axon bundle containing neuronal processes of sensory and interneurons which form connections (synapses) as they run next to each other.. The invariant ...
foxP2, a forkhead-domain transcription factor, is critical for speech and language development in humans, but its role in the establishment of CNS connectivity is unclear. While in vitro studies have identified axon guidance molecules as targets of foxP2 regulation, and cell culture assays suggest a role for foxP2 in neurite outgrowth, in vivo studies have been lacking regarding a role for foxP2 in axon pathfinding. We used a modified zinc finger nuclease methodology to generate mutations in the zebrafish foxP2 gene. Using PCR-based high resolution melt curve analysis (HRMA) of G0 founder animals, we screened and identified three mutants carrying nonsense mutations in the 2nd coding exon: a 17 base-pair (bp) deletion, an 8bp deletion, and a 4bp insertion. Sequence analysis of cDNA confirmed that these were frameshift mutations with predicted early protein truncations. Homozygous mutant fish were viable and fertile, with unchanged body morphology, and no apparent differences in CNS apoptosis,
View more ,The process of establishing long-range neuronal connections can be divided into at least three discrete steps. First, axons need to be stimulated to grow and this growth must be towards appropriate targets. Second, after arriving at their target, axons need to be directed to their topographically appropriate position and in some cases, such as in cortical structures, they must grow radially to reach the correct laminar layer. Third, axons then arborize and form synaptic connections with only a defined subpopulation of potential post-synaptic partners. Attempts to understand these mechanisms in the visual system have been ongoing since pioneer studies in the 1940s highlighted the specificity of neuronal connections in the retino-tectal pathway. These classical systems-based approaches culminated in the 1990s with the discovery that Eph-ephrin repulsive interactions were involved in topographical mapping. In marked contrast, it was the cloning of the odorant receptor family that quickly ...
In recent years, it has been demonstrated that mRNAs localize to axons of young and mature central and peripheral nervous system neurons in culture and in vivo. Increasing evidence is supporting a fundamental role for the local translation of these mRNAs in neuronal function by regulating axon growth, maintenance and ... read more regeneration after injury. Although most mRNAs found in axons are abundant transcripts and not restricted to the axonal compartment, they are sequestered into transport ribonucleoprotein particles and their axonal localization is likely the result of specific targeting rather than passive diffusion. It has been reported that long-distance mRNA transport requires microtubule-dependent motors, but the molecular mechanisms underlying the sorting and trafficking of mRNAs into axons have remained elusive. This review places particular emphasis on motor-dependent transport of mRNAs and presents a mathematical model that describes how microtubule-dependent motors can achieve ...
In this simulation action potential initiation, action potential properties and the role of axon initial segment Na+ channels are investigated in a realistic model of a layer 5 pyramidal neuron axon initial segment. The main Na+ channel properties were constrained by experimental data and the axon initial segment was reconstructed. Model parameters were constrained by direct recordings at the axon initial segment ...
The spatial and temporal regulation of calcium signaling in neuronal growth cones is essential for axon guidance. In growth cones, the endoplasmic reticulum (ER) is a significant source of calcium signals. However, it is not clear whether the ER is remodeled during motile events to localize calcium signals in steering growth cones. The expression of the ER-calcium sensor, stromal interacting molecule 1 (STIM1) is necessary for growth cone steering toward the calcium-dependent guidance cue BDNF, with STIM1 functioning to sustain calcium signals through store-operated calcium entry. However, STIM1 is also required for growth cone steering away from semaphorin-3a, a guidance cue that does not activate ER-calcium release, suggesting multiple functions of STIM1 within growth cones (Mitchell et al. 2012). STIM1 also interacts with microtubule plus-end binding proteins EB1/EB3 (Grigoriev et al. 2008). Here, we show that STIM1 associates with EB1/EB3 in growth cones and that STIM1 expression is critical ...
Knockdown of RacGAP50C in MB neurons results in reduction of cell number and axon overextension (Fig. 1B ). The enlarged cells and reduction of neurons derived from the Nbs are reminiscent of cytokinesis defects seen in MB neurons that are homozygous mutant for small GTPase RhoA (25) and is consistent with previous work identifying RacGAP50C and its homologues as a critical regulator of cytokinesis (8-12). In addition to the cytokinetic phenotype, the normal axon trajectory is disrupted with RacGAP50C reduction. Dorsal projecting axon branches are normally confined within a morphologically distinct dorsal lobe that extends toward the dorsal surface of the brain (Fig. 1A ). However, with reduced RacGAP50C, axons extend beyond the dorsal lobe and project toward the midline of the brain (arrowheads in Fig. 1B , and Fig. 1C ). Occasionally, processes also target incorrectly and extend ventromedially from the dendritic region of the MB (#s in Fig. 1B ). This phenotype suggests a previously ...
Vertebrate branchial nerves, i.e., the Vth, VIIth, IXth, and Xth cranial nerves, have neural crest-derived and placode-derived sensory neurons in their proximal and distal ganglia, respectively [18]. These nerves also have motor neurons, the cell bodies of which lie in the ventral hindbrain; and their axons project to the branchial arches through proximal and distal ganglia during development [39]. The sensory ganglia of these nerves are known to be weakly chemoattractive for motor neurons, as shown in co-culture experiments [40]. It is known that placode-derived neurons differentiate earlier than neural crest-derived ones [41, 42] and that in embryos where the placodes have been removed, the axonal projection pattern of proximal ganglion neurons to the periphery is defective [43]. These findings suggest that proper developmental regulation of the placode-derived neurons should be required for all 3 types of branchial nerve neurons, i.e., the 2 sensory types (neural crest-derived and ...
Normal brain function depends on the development of appropriate patterns of neural connections. A critical role in guiding axons to their targets during neural development is played by neuronal growth cones. These have a complex and rapidly changing morphology; however, a quantitative understanding of this morphology, its dynamics and how these are related to growth cone movement, is lacking. Here we use eigenshape analysis (principal components analysis in shape space) to uncover the set of five to six basic shape modes that capture the most variance in growth cone form. By analysing how the projections of growth cones onto these principal modes evolve in time, we found that growth cone shape oscillates with a mean period of 30 min. The variability of oscillation periods and strengths between different growth cones was correlated with their forward movement, such that growth cones with strong, fast shape oscillations tended to extend faster. A simple computational model of growth cone shape dynamics
Axon degeneration is a characteristic feature of multiple neuropathologic states and is also a mechanism of physiological neurodevelopmental pruning. The vast majority of in vivo studies looking at axon degeneration have relied on the use of classical silver degeneration stains, which have many limitations including lack of molecular specificity and incompatibility with immunolabeling methods. Because Wallerian degeneration is well known to involve cytoskeletal disassembly and because caspases are recently implicated in aspects of this process, we asked whether antibodies directed at caspase-generated neoepitopes of beta-actin and alpha-tubulin would be useful immunohistochemical markers of pathological and developmental axon degeneration. Here we demonstrate that several forms of axon degeneration involve caspase-mediated cleavage of these cytoskeletal elements and are well-visualized using this approach. We demonstrate the generation of caspase-induced neoepitopes in a) an in vitro neuronal culture
Inactivation of the sodium current in squid giant axons by hydrocarbons.: The voltage dependence of the steady state inactivation parameter (h infinity) of the
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GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis. May also regulate Golgi biogenesis. May regulate axonal development.
The aim of this study was to evaluate changes in sensory axonal excitability in the distal nerve in patients with cervical radiculopathy. The patients were classified by the findings of cervical MRI into two subgroups: 22 patients with C6/7 roo
www.MOLUNA.de New Aspects of Axonal Structure and Function [4212751] - A summary of recent findings covering the morphological, physiological, developmental, computational and pathophysiological aspects of axons, this volume covers new findings concerning axonal structure and functions and assesses their implications.nAxons are neuronal output elements and are responsible for the transfer and processing of signals from one neuron to another, even
Abstract: Axotomy-induced degradation of retinal ganglion cells (RGC) can be delayed if the destructive features of activated Microglial cells are pharmacologically neutralized, and prevented if the axons are permitted to regrow into transplanted autologous peripheral nerve (PN) pieces. Axotomized central nervous system neurons, whose regenerating axons are guided to their natural target areas in the brain with the aid of PN grafts, are capable of establishing synaptic contacts with normal morphological and electrophysiological properties. This study was undertaken to 1) morphometrically characterize and classify the regenerating rat RGC, 2) examine target-dependent effects on survival of subsets of neurons, and 3) investigate whether reconnected neurons are capable of restoring visual functions. In analogy to the normal rat retina, as a first step, the retrogradely labeled, regenerating RGC were categorized into five classes which are morphologically distinct and reminiscent of normal RGC ...
Adenomatous polyposis coli (APC) is a microtubule plus-end scaffolding protein important in biology and disease. APC is implicated in RNA localization, although the mechanisms and functional significance remain unclear. We show APC is an RNA-binding protein and identify an RNA interactome by HITS-CLIP. Targets were highly enriched for APC-related functions, including microtubule organization, cell motility, cancer, and neurologic disease. Among the targets is β2B-tubulin, known to be required in human neuron and axon migration. We show β2B-tubulin is synthesized in axons and localizes preferentially to dynamic microtubules in the growth cone periphery. APC binds the β2B-tubulin 3 UTR; experiments interfering with this interaction reduced β2B-tubulin mRNA axonal localization and expression, depleted dynamic microtubules and the growth cone periphery, and impaired neuron migration. These results identify APC as a platform binding functionally related protein and RNA networks, and suggest a ...
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