共查询到20条相似文献，搜索用时 406 毫秒
1.
The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC (Deleted in Colorectal Cancer). We have found that chemical inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth in vitro. We have also found that DCC is a substrate for metalloprotease-dependent ectodomain shedding, and that the inhibitors block proteolytic processing of DCC and cause an increase in DCC protein levels on axons within spinal cord explants. Thus, potentiation of netrin activity by inhibitors may result from stabilization of DCC on the axons, and proteolytic activity may regulate axon migration by controlling the number of functional extracellular axon guidance receptors. 相似文献
2.
Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway 总被引：15，自引：0，他引：15
Regenerating sensory axons in the dorsal roots of adult mammals are stopped at the junction between the root and spinal cord by reactive astrocytes. Do these cells stop axonal elongation by activating the physiological mechanisms that normally operate to stop axons during development, or do they physically obstruct the elongating axons? In order to distinguish these possibilities, the cytology of the axon tips of regenerating axons that were stopped by astrocytes was compared with the axon tips that were physically obstructed at a cul-de-sac produced by ligating a peripheral nerve. The terminals of the physically obstructed axon tips were distended with neurofilaments and other axonally transported structures that had accumulated when the axons stopped elongating. By contrast, neurofilaments did not accumulate in the tips of regenerating axons that were stopped by spinal cord astrocytes at the dorsal root transitional zone. These axo-glial terminals resembled the terminals that axons make on target neurons during normal development. On the basis of these observations, astrocytes appear to stop axons from regenerating in the mammalian spinal cord by activating the physiological stop pathway that is built into the axon and that normally operates when axons form stable terminals on target cells. 相似文献
3.
Axonal proteins of presynaptic neurons during synaptogenesis 总被引：5，自引：0，他引：5
P Sonderegger M C Fishman M Bokoum H C Bauer P G Nelson 《Science (New York, N.Y.)》1983,221(4617):1294-1297
Changes occur in the synthesis and axonal transport of neuronal proteins in dorsal-root ganglia axons as a result of contact with cells from the spinal cord during synapse formation. Dorsal-root ganglia cells were cultured in a compartmental cel culture system that allows separate access to neuronal cell bodies and their axons. When cells from the ventral spinal cord were cultured with the dorsal-root ganglia axons, synapses were established within a few days. Metabolic labeling and two-dimensional electrophoresis revealed that four of more than 300 axonal proteins had changed in their expression by the time synapses were established. The highly selective nature of these changes suggests that the proteins involved may be important in the processes of axon growth and synapse formation and their regulation by the regional environment. 相似文献
4.
DNA topoisomerase IIbeta is shown to have an unsuspected and critical role in neural development. Neurogenesis was normal in IIbeta mutant mice, but motor axons failed to contact skeletal muscles, and sensory axons failed to enter the spinal cord. Despite an absence of innervation, clusters of acetylcholine receptors were concentrated in the central region of skeletal muscles, thereby revealing patterning mechanisms that are autonomous to skeletal muscle. The defects in motor axon growth in IIbeta mutant mice resulted in a breathing impairment and death of the pups shortly after birth. 相似文献
5.
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
6.
Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation
Netrins stimulate and orient axon growth through a mechanism requiring receptors of the DCC family. It has been unclear, however, whether DCC proteins are involved directly in signaling or are mere accessory proteins in a receptor complex. Further, although netrins bind cells expressing DCC, direct binding to DCC has not been demonstrated. Here we show that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor, proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation. 相似文献
7.
Lyuksyutova AI Lu CC Milanesio N King LA Guo N Wang Y Nathans J Tessier-Lavigne M Zou Y 《Science (New York, N.Y.)》2003,302(5652):1984-1988
Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed source of Wnt4 protein attracted postcrossing commissural axons. Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior-posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord. 相似文献
8.
Helmuth L 《Science (New York, N.Y.)》2000,289(5479):521-522
On page 628, neuroscientists report that painful stimuli delivered to rats shortly after birth permanently rewire the spinal cord circuits that respond to pain. Not only do the circuits contain more axons, but the axons extend to more areas of the spinal cord than they normally would. The results should help convince skeptics of the importance of managing pain in human infants. 相似文献
9.
为了研究微管相关蛋白2(M AP 2)在促进微管形成、维持微管稳定及促进轴突和树突细胞器转运等方面的作用,试验克隆了M AP 2微管结合区基因,构建了原核表达载体pET 32a-M AP 2并对其进行诱导表达,利用亲和层析法对表达产物进行纯化,研究了表达产物与微管蛋白之间的作用。结果表明,融合表达的人M AP 2微管结合区蛋白约43 ku,可与天然的微管蛋白发生分子间的结合作用,为M AP 2生理功能的研究奠定了基础。 相似文献
10.
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
11.
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
12.
Axons from eyes transplanted to the tail in Xenopus larvae enter the caudal spinal cord and follow two adjacent tracts rostrally to the level of the cerebellum. When eyes are transplanted to the ear area, optic axons enter the hindbrain and follow the same tracts rostrally and caudally. These sensory pathways normally contain the embryonic sensory system of the Rohon-Beard axons and the descending and ascending tracts of nerve V. We propose that the transplanted optic axons have followed a continuous substrate sensory pathway normally shared by a number of different sensory tracts. 相似文献
13.
Park KK Liu K Hu Y Smith PD Wang C Cai B Xu B Connolly L Kramvis I Sahin M He Z 《Science (New York, N.Y.)》2008,322(5903):963-966
The failure of axons to regenerate is a major obstacle for functional recovery after central nervous system (CNS) injury. Removing extracellular inhibitory molecules results in limited axon regeneration in vivo. To test for the role of intrinsic impediments to axon regrowth, we analyzed cell growth control genes using a virus-assisted in vivo conditional knockout approach. Deletion of PTEN (phosphatase and tensin homolog), a negative regulator of the mammalian target of rapamycin (mTOR) pathway, in adult retinal ganglion cells (RGCs) promotes robust axon regeneration after optic nerve injury. In wild-type adult mice, the mTOR activity was suppressed and new protein synthesis was impaired in axotomized RGCs, which may contribute to the regeneration failure. Reactivating this pathway by conditional knockout of tuberous sclerosis complex 1, another negative regulator of the mTOR pathway, also leads to axon regeneration. Thus, our results suggest the manipulation of intrinsic growth control pathways as a therapeutic approach to promote axon regeneration after CNS injury. 相似文献
14.
Structure of the giant fibers of earthworms 总被引：1，自引：0，他引：1
B Mulloney 《Science (New York, N.Y.)》1970,168(934):994-996
The median giant fiber and the pair of lateral giant fibers that run the length of the ventral nerve cord in earthworms were thought to arise by fusion of the axons of several nerve cells in each segment. The structure of these giant fibers has now been examined with a fluorescent dye injected into single fibers. Each giant axon connects to one cell body in each segment; the giant fibers are not fused axons. In each segment, the median giant fiber has three branches and each lateral giant fiber has five branches. These branches are presumably dendritic. No structural differences between the giant fibers in anterior and posterior regions of the worm seem to account for the functional polarity of the giant fiber system observed in behavioral studies. 相似文献
15.
Wilson DM 《Science (New York, N.Y.)》1959,129(3352):841-842
Unit spikes were recorded from the spinal cord of the lungfish Protopterus and were identified with Mauthner's axon. With these spikes occurred nongraded tail flips suggesting startle responses. The tail flip and the giant spike resulted from certain forms of jarring and prodding. The conduction velocity for the slightly myelinated. 45 micro diameter fibers was 18.5 m/sec. 相似文献
16.
The role of localized instability of the actin network in specifying axonal fate was examined with the use of rat hippocampal neurons in culture. During normal neuronal development, actin dynamics and instability polarized to a single growth cone before axon formation. Consistently, global application of actin-depolymerizing drugs and of the Rho-signaling inactivator toxin B to nonpolarized cells produced neurons with multiple axons. Moreover, disruption of the actin network in one individual growth cone induced its neurite to become the axon. Thus, local instability of the actin network restricted to a single growth cone is a physiological signal specifying neuronal polarization. 相似文献
17.
18.
Athale CA Dinarina A Mora-Coral M Pugieux C Nedelec F Karsenti E 《Science (New York, N.Y.)》2008,322(5905):1243-1247
During spindle assembly, chromosomes generate gradients of microtubule stabilization through a reaction-diffusion process, but how this is achieved is not well understood. We measured the spatial distribution of microtubule aster asymmetry around chromosomes by incubating centrosomes and micropatterned chromatin patches in frog egg extracts. We then screened for microtubule stabilization gradient shapes that would generate such spatial distributions with the use of computer simulations. Only a long-range, sharply decaying microtubule stabilization gradient could generate aster asymmetries fitting the experimental data. We propose a reaction-diffusion model that combines the chromosome generated Ran-guanosine triphosphate-Importin reaction network to a secondary phosphorylation network as a potential mechanism for the generation of such gradients. 相似文献
19.
Fricke C Lee JS Geiger-Rudolph S Bonhoeffer F Chien CB 《Science (New York, N.Y.)》2001,292(5516):507-510
As growing retinotectal axons navigate from the eye to the tectum, they sense guidance molecules distributed along the optic pathway. Mutations in the zebrafish astray gene severely disrupt retinal axon guidance, causing anterior-posterior pathfinding defects, excessive midline crossing, and defasciculation of the retinal projection. Eye transplantation experiments show that astray function is required in the eye. We identify astray as zebrafish robo2, a member of the Roundabout family of axon guidance receptors. Retinal ganglion cells express robo2 as they extend axons. Thus, robo2 is required for multiple axon guidance decisions during establishment of the vertebrate visual projection. 相似文献
20.
鸡腔上囊传出神经元的分布——用CB—HRP法研究 总被引：6，自引：0，他引：6
将CB—HRP注入鸡腔上囊壁内,支配腔上囊的神经元被标记。支配腔上囊的长轴突型交感节前神经元在胸7—腰荐3(简称T_7—LS_3)髓节的Terni氏柱内,主要位于LS_1—LS_2髓节。在LS_8—LS_(11)髓节中央管背侧和背外侧区有大量标记细胞,主要集中于LS_8髓节,这些标记细胞是支配腔上囊的副交感节前神经元,其轴突大部分行经同侧盆神经到达腔上囊,少数行经对侧的盆神经到达腔上囊。腔上囊的交感节后神经元位于T_6—L_(13)交感干神经节和肾上腺神经节,交感干的标记细胞集中位于LS_9—LS_(11)和LS_2—LS_3。副交感节后神经元位于盆神经和泄殖腔神经节内。在肠神经内有大量的标记细胞。 相似文献