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1.
Grasshopper neurons accurately project axons across long distances between peripheral structures and the central nervous system. Nerve-trunk pathways followed by these axons are established early in embryogenesis by pioneer neurons. Growth cones from the first pioneers navigate along a chain of cells to the CNS. The placement of these cells may constitute the initial guidance mechanism underlying long-distance pathfinding. 相似文献
2.
J Y Kuwada 《Science (New York, N.Y.)》1986,233(4765):740-746
The mechanism that guides neuronal growth cones to their targets in vertebrate embryos has been difficult to study primarily because of the complexity and large number of neurons found in many vertebrate nervous systems. The spinal cord of a simple vertebrate, the fish embryo, is used to analyze pathfinding mechanisms. The early embryonic spinal cord consists of a relatively small number of identifiable neurons. From the beginning of axonal outgrowth the growth cones of these identified neurons extend along stereotyped and precise pathways in the spinal cord. Laser ablation experiments (i) support the hypothesis that early growth cones that pioneer specific spinal tracts appear to recognize cues on subsets of longitudinally arrayed neuroepithelial cells and (ii) demonstrate that later growth cones that selectively fasciculate in these spinal tracts appear to recognize cues on specific subsets of axons. 相似文献
3.
Neurotrophins regulate survival, axonal growth, and target innervation of sensory and other neurons. Neurotrophin-3 (NT-3) is expressed specifically in cells adjacent to extending axons of dorsal root ganglia neurons, and its absence results in loss of most of these neurons before their axons reach their targets. However, axons are not required for NT-3 expression in limbs; instead, local signals from ectoderm induce NT-3 expression in adjacent mesenchyme. Wnt factors expressed in limb ectoderm induce NT-3 in the underlying mesenchyme. Thus, epithelial-mesenchymal interactions mediated by Wnt factors control NT-3 expression and may regulate axonal growth and guidance. 相似文献
4.
Cell recognition during neuronal development 总被引：20，自引：0，他引：20
C S Goodman M J Bastiani C Q Doe S du Lac S L Helfand J Y Kuwada J B Thomas 《Science (New York, N.Y.)》1984,225(4668):1271-1279
Insect embryos, with their relatively simple nervous systems, provide a model system with which to study the cellular and molecular mechanisms underlying cell recognition during neuronal development. Such an approach can take advantage of the accessible cells of the grasshopper embryo and the accessible genes of Drosophila. The growth cones of identified neurons express selective affinities for specific axonal surfaces; such specificities give rise to the stereotyped patterns of selective fasciculation common to both species. These and other results suggest that early in development cell lineage and cell interactions lead to the differential expression of cell recognition molecules on the surfaces of small subsets of embryonic neurons whose axons selectively fasciculate with one another. Monoclonal antibodies reveal surface molecules in the Drosophila embryo whose expression correlates with this prediction. It should now be possible to isolate the genes encoding these potential cell recognition molecules and to test their function through the use of molecular genetic approaches in Drosophila. 相似文献
5.
Hellal F Hurtado A Ruschel J Flynn KC Laskowski CJ Umlauf M Kapitein LC Strikis D Lemmon V Bixby J Hoogenraad CC Bradke F 《Science (New York, N.Y.)》2011,331(6019):928-931
Hypertrophic scarring and poor intrinsic axon growth capacity constitute major obstacles for spinal cord repair. These processes are tightly regulated by microtubule dynamics. Here, moderate microtubule stabilization decreased scar formation after spinal cord injury in rodents through various cellular mechanisms, including dampening of transforming growth factor-β signaling. It prevented accumulation of chondroitin sulfate proteoglycans and rendered the lesion site permissive for axon regeneration of growth-competent sensory neurons. Microtubule stabilization also promoted growth of central nervous system axons of the Raphe-spinal tract and led to functional improvement. Thus, microtubule stabilization reduces fibrotic scarring and enhances the capacity of axons to grow. 相似文献
6.
An important question in developmental neurobiology is how a neuron finds its way over long distances to its correct target during embryogenesis. Peripheral pioneer neurons in insect embryos have been used for study because of the relative simplicity of the early embryonic appendages, and the accessibility of the identified neurons whose growth cones traverse this terrain. The data presented suggest an adhesive hierarchy of both epithelial and neuronal surfaces that guides the first growth cones from the appendages of the grasshopper embryo. 相似文献
7.
Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats 总被引：48，自引：0，他引：48
The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as "bridges" between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system. 相似文献
8.
Axonal regeneration in the adult central nervous system (CNS) is limited by two proteins in myelin, Nogo and myelin-associated glycoprotein (MAG). The receptor for Nogo (NgR) has been identified as an axonal glycosyl-phosphatidyl-inositol (GPI)-anchored protein, whereas the MAG receptor has remained elusive. Here, we show that MAG binds directly, with high affinity, to NgR. Cleavage of GPI-linked proteins from axons protects growth cones from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of neurite outgrowth. MAG-resistant embryonic neurons are rendered MAG-sensitive by expression of NgR. MAG and Nogo-66 activate NgR independently and serve as redundant NgR ligands that may limit axonal regeneration after CNS injury. 相似文献
9.
Subplate neurons pioneer the first axon pathway from the cerebral cortex 总被引：28，自引：0，他引：28
During the development of the nervous system, growing axons must traverse considerable distances to find their targets. In insects, this problem is solved in part by pioneer neurons, which lay down the first axonal pathways when distances are at a minimum. Here the existence of a similar kind of neuron in the developing mammalian telencephalon is described. These are the subplate cells, the first postmitotic neurons of the cerebral cortex. Axons from subplate neurons traverse the internal capsule and invade the thalamus early in fetal life, even before the neurons of cortical layers 5 and 6, which will form the adult subcortical projections, are generated. During postnatal life, after the adult pattern of axonal projections is firmly established, most subplate neurons disappear. These observations raise the possibility that the early axonal scaffold formed by subplate cells may prove essential for the establishment of permanent subcortical projections. 相似文献
10.
Berghuis P Rajnicek AM Morozov YM Ross RA Mulder J Urbán GM Monory K Marsicano G Matteoli M Canty A Irving AJ Katona I Yanagawa Y Rakic P Lutz B Mackie K Harkany T 《Science (New York, N.Y.)》2007,316(5828):1212-1216
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB(1)R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo. 相似文献
11.
Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions 总被引：1，自引：0，他引：1
Marín O Yaron A Bagri A Tessier-Lavigne M Rubenstein JL 《Science (New York, N.Y.)》2001,293(5531):872-875
Most striatal and cortical interneurons arise from the basal telencephalon, later segregating to their respective targets. Here, we show that migrating cortical interneurons avoid entering the striatum because of a chemorepulsive signal composed at least in part of semaphorin 3A and semaphorin 3F. Migrating interneurons expressing neuropilins, receptors for semaphorins, are directed to the cortex; those lacking them go to the striatum. Loss of neuropilin function increases the number of interneurons that migrate into the striatum. These observations reveal a mechanism by which neuropilins mediate sorting of distinct neuronal populations into different brain structures, and provide evidence that, in addition to guiding axons, these receptors also control neuronal migration in the central nervous system. 相似文献
12.
A protein induced during nerve growth (GAP-43) is a major component of growth-cone membranes 总被引：24，自引：0，他引：24
J H Skene R D Jacobson G J Snipes C B McGuire J J Norden J A Freeman 《Science (New York, N.Y.)》1986,233(4765):783-786
Growth cones are specialized structures that form the distal tips of growing axons. During both normal development of the nervous system and regeneration of injured nerves, growth cones are essential for elongation and guidance of growing axons. Developmental and regenerative axon growth is frequently accompanied by elevated synthesis of a protein designated GAP-43. GAP-43 has now been found to be a major component of growth-cone membranes in developing rat brains. Relative to total protein, GAP-43 is approximately 12 times as abundant in growth-cone membranes as in synaptic membranes from adult brains. Immunohistochemical localization of GAP-43 in frozen sections of developing brain indicates that the protein is specifically associated with neuropil areas containing growth cones and immature synaptic terminals. The results support the proposal that GAP-43 plays a role in axon growth. 相似文献
13.
Neuronal cytomechanics: the actin-based motility of growth cones 总被引：43，自引：0，他引：43
S J Smith 《Science (New York, N.Y.)》1988,242(4879):708-715
The patterns of synaptic connection that underlie brain function depend on the elaborate forms characteristic of neurons. It is therefore a central goal of neuroscience to understand the molecular basis for neuronal shape. Neuronal pathfinding during development is one major determinant of neuronal shape: growing nerve axons and dendrites must navigate, branch, and locate targets in response to extracellular cue molecules within the embryo. The leading tips of growing nerve processes, structures known as growth cones, contain especially high concentrations of the ubiquitous mechanochemical protein actin. Force generation involving this cytoskeletal molecule appears to be essential to the ability of growing nerve fibers to respond structurally to extracellular cues. New results from electronically enhanced light microscopy of living growth cones are helping to show how actin-based forces guide neurite growth and synapse formation. 相似文献
14.
Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: They become repelled by the repellent Slit and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attractive environment appear repulsive. Here, we provide evidence that these two changes are causally linked: In the growth cones of embryonic Xenopus spinal axons, activation of the Slit receptor Roundabout (Robo) silences the attractive effect of netrin-1, but not its growth-stimulatory effect, through direct binding of the cytoplasmic domain of Robo to that of the netrin receptor DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug-of-war between attractive and repulsive signals in the growth cone that might cause confusion. Molecularly, silencing is enabled by a modular and interlocking design of the cytoplasmic domains of these potentially antagonistic receptors that predetermines the outcome of their simultaneous activation. 相似文献
15.
GAP-43 is one of a small subset of cellular proteins selectively transported by a neuron to its terminals. Its enrichment in growth cones and its increased levels in developing or regenerating neurons suggest that it has an important role in neurite growth. A complementary DNA (cDNA) that encodes rat GAP-43 has been isolated to study its structural characteristics and regulation. The predicted molecular size is 24 kilodaltons, although its migration in SDS-polyacrylamide gels is anomalously retarded. Expression of GAP-43 is limited to the nervous system, where its levels are highest during periods of neurite outgrowth. Nerve growth factor or adenosine 3',5'-monophosphate induction of neurites from PC12 cells is accompanied by increased GAP-43 expression. GAP-43 RNA is easily detectable, although at diminished levels, in the adult rat nervous system. This regulation of GAP-43 is concordant with a role in growth-related processes of the neuron, processes that may continue in the mature animal. 相似文献
16.
Zou DJ Feinstein P Rivers AL Mathews GA Kim A Greer CA Mombaerts P Firestein S 《Science (New York, N.Y.)》2004,304(5679):1976-1979
Axonal projections from the olfactory epithelium to the olfactory bulb are organized into glomeruli according to the expressed odorant receptor. Using gene-targeted mice, we show that glomerular maturation proceeds along different time courses for two similar receptors and requires sensory input during distinct sensitive periods. During early development, some glomeruli are innervated by axons of neurons that do not express the same receptor. These heterogeneous glomeruli normally disappear with age, but they persist in adults deprived of sensory input by unilateral and permanent naris closure. Persistence may be due, in part, to prolonged survival of olfactory sensory neurons. 相似文献
17.
Zhou L Bar I Achouri Y Campbell K De Backer O Hebert JM Jones K Kessaris N de Rouvroit CL O'Leary D Richardson WD Goffinet AM Tissir F 《Science (New York, N.Y.)》2008,320(5878):946-949
Development of axonal tracts requires interactions between growth cones and the environment. Tracts such as the anterior commissure and internal capsule are defective in mice with null mutation of Celsr3. We generated a conditional Celsr3 allele, allowing regional inactivation. Inactivation in telencephalon, ventral forebrain, or cortex demonstrated essential roles for Celsr3 in neurons that project axons to the anterior commissure and subcerebral targets, as well as in cells that guide axons through the internal capsule. When Celsr3 was inactivated in cortex, subcerebral projections failed to grow, yet corticothalamic axons developed normally, indicating that besides guidepost cells, additional Celsr3-independent cues can assist their progression. These observations provide in vivo evidence that Celsr3-mediated interactions between axons and guidepost cells govern axonal tract formation in mammals. 相似文献
18.
TA Jarrell Y Wang AE Bloniarz CA Brittin M Xu JN Thomson DG Albertson DH Hall SW Emmons 《Science (New York, N.Y.)》2012,337(6093):437-444
In order to understand the nervous system, it is necessary to know the synaptic connections between the neurons, yet to date, only the wiring diagram of the adult hermaphrodite of the nematode Caenorhabditis elegans has been determined. Here, we present the wiring diagram of the posterior nervous system of the C. elegans adult male, reconstructed from serial electron micrograph sections. This region of the male nervous system contains the sexually dimorphic circuits for mating. The synaptic connections, both chemical and gap junctional, form a neural network with four striking features: multiple, parallel, short synaptic pathways directly connecting sensory neurons to end organs; recurrent and reciprocal connectivity among sensory neurons; modular substructure; and interneurons acting in feedforward loops. These features help to explain how the network robustly and rapidly selects and executes the steps of a behavioral program on the basis of the inputs from multiple sensory neurons. 相似文献
19.
The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system was previously unknown. We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth. Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat cerebellum in vivo revealed cell-autonomous abnormalities in layer-specific growth of granule neuron axons and parallel fiber patterning. Cdh1 RNA interference in neurons was also found to override the inhibitory influence of myelin on axonal growth. Thus, Cdh1-APC appears to play a role in regulating axonal growth and patterning in the developing brain that may also limit the growth of injured axons in the adult brain. 相似文献
20.
Ants of the ponerine genus Odontomachus use a trap jaw mechanism when hunting fast prey. When particular trigger hairs, located on the inner edge of the mandibles, are touched by prey, the jaws close extremely rapidly and trap the target. This trap jaw response lasts only 0.33 to 1 millisecond. Electrophysiological recordings demonstrated that the trigger hairs function as mechanoreceptors. Associated with each trigger hair are large sensory cells, the sensory axons of which measure 15 to 20 micrometers in diameter. These are among the largest sensory neurons, and their size implies that these axons conduct information very rapidly. 相似文献