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1.
G. Tear 《Cellular and molecular life sciences : CMLS》1999,55(11):1365-1376
A key feature of the central nervous system of most higher organisms is their bilateral symmetry about the midline. The specialised
cells that lie at the midline have an essential role in regulating the axon guidance decisions of both neurons that project
axons across the midline and those that project on one side. The midline cells produce both attractive and repellent short-
and long-range signals to guide axonal growth. The axons themselves express specific receptors that can be dynamically regulated
in response to midline-derived signals. In this way, axons extend toward or away from the midline and those that do cross
change their behaviour to respond to longitudinal signals on the contralateral side. 相似文献
2.
T. P. O’Connor 《Cellular and molecular life sciences : CMLS》1999,55(11):1358-1364
Neurons must often extend axons over fairly long distances, making multiple changes in their trajectory of growth before
arriving at their final target. It has become clear that as growth cones navigate these complex projections, they typically
extend toward a number of intermediate targets before they contact their final target. Recent work from a variety of systems
has identified intermediate targets that seem to play similar roles in vertebrate and invertebrate nervous system development.
From these examples it appears that a general model of axon guidance can be proposed whereby neurons are guided to their targets
segmentally. Within each segment, an intermediate target appears to be the primary target for growth cone recognition and
thus the completion of the journey to the final target is determined by a series of successful segmental pathfinding decisions. 相似文献
3.
P. A. Garrity 《Cellular and molecular life sciences : CMLS》1999,55(11):1407-1415
Neurons establish specific connections by extending projections to contact their targets. Projections, such as axons, navigate
to the target by sensing guidance cues in their environment and responding with directed movement and shape change. The recent
identification of the molecular identities of many guidance cues and guidance receptors has demonstrated that axons are guided
to their targets by combinations of cues that attract and repel them. The current challenge is to elucidate how these guidance
cue/receptor interactions control navigation. This review focuses on recent progress in identifying the signaling pathways
downstream of these receptors and in determining why an axon is attracted or repelled by a particular guidance cue. 相似文献
4.
5.
Wnt signaling: multiple functions in neural development 总被引:11,自引:0,他引:11
Wnt signaling has proven to be essential for neural development at various stages and across species. Wnts are involved in morphogenesis and patterning, and their proliferation-promoting role is a key function in stem cell maintenance and the expansion of progenitor pools. Moreover, Wnt signaling is involved in differentiation processes and lineage decision events during both central and peripheral nervous system development. Additionally, several reports point to a role of Wnt signaling in axon guidance and neurite outgrowth. This article reviews and consolidates the existing evidence for the functions of Wnt signaling in neural development.Received 10 December 2004; received after revision 19 January 2005; accepted 21 January 2005 相似文献
6.
7.
Plexins: axon guidance and signal transduction 总被引:6,自引:2,他引:4
Axon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as semaphorins, ephrins and netrin. Plexins function as receptors for the repulsive axonal guidance molecules semaphorins. Intracellular domains of plexins are responsible for initiating cellular signal transduction inducing axon repulsion. Recent advances have revealed molecular mechanisms for plexin-mediated cytoskeletal reorganization, leading to repulsive responses, and small GTPases play important roles in this signaling. Plexin-B1 activates Rho through Rho-specific guanine nucleotide exchange factors, leading to neurite retraction. Plexin-B1 possesses an intrinsic GTPase-activating protein activity for R-Ras and induces growth cone collapse through R-Ras inactivation. In this review we survey current understanding of the signaling mechanisms of plexins.Received 13 January 2005; received after revision 3 February 2005; accepted 15 February 2005 相似文献
8.
Formation of myelin sheaths by Schwann cells (SCs) enables rapid and efficient transmission of action potentials in peripheral axons, and disruption of myelination results in disorders that involve decreased sensory and motor functions. Given that construction of SC myelin requires high levels of lipid and protein synthesis, mitochondria, which are pivotal in cellular metabolism, may be potential regulators of the formation and maintenance of SC myelin. Supporting this notion, abnormal mitochondria are found in SCs of neuropathic peripheral nerves in both human patients and the relevant animal models. However, evidence for the importance of SC mitochondria in myelination has been limited, until recently. Several studies have recently used genetic approaches that allow SC-specific ablation of mitochondrial metabolic activity in living animals to show the critical roles of SC mitochondria in the development and maintenance of peripheral nerve axons. Here, we review current knowledge about the involvement of SC mitochondria in the formation and dysfunction of myelinated axons in the peripheral nervous system. 相似文献
9.
Strotmann J 《Cellular and molecular life sciences : CMLS》2001,58(4):531-537
Olfactory sensory neurons detect an enormous variety of small volatile molecules with extremely high sensitivity and specificity.
The actual recognition and discrimination of odorous compounds is accomplished by specific receptor proteins located in the
ciliary membrane of the sensory neurons. Axonal connections into the olfactory bulb, the first relay station for odor processing
in the brain, are organized such that all neurons expressing the same odorant receptor converge their axons onto common glomeruli
which are located at similar positions in all individuals from one species. For the establishment of this precise targeting
of olfactory axons to their appropriate glomeruli, combinatorial functions of axon-associated cell adhesion molecules and
odorant receptor proteins appear to be required. Odorants that stimulate distinct receptor cell populations will thereby activate
a specific combination of glomeruli in the bulb; this characteristic activity pattern may be used by the system to encode
the quality of a particular odorant. 相似文献
10.
Netrins and netrin receptorsRID="†"ID="†" Review 总被引:5,自引:0,他引:5
Livesey FJ 《Cellular and molecular life sciences : CMLS》1999,56(1-2):62-68
The formation of precise connections between neurons and their targets during development is dependent on extracellular guidance cues that allow growing axons to navigate to their targets. One family of such guidance molecules. conserved across all species examined, is that of the netrin/UNC-6 proteins. Netrins act to both attract and repel the growing axons of a broad range of neuronal cell types during development and are also involved in controling neuronal cell migration. These actions are mediated by specific receptor complexes containing either the colorectal cancer (DCC) or neogenin protein, in the case of the attractive receptor, or UNC-5-related proteins, in the case of the repellent receptor. Recent work has identified a key role for intracellular cyclic nucleotide levels in regulating the nature of the response of the growing axon to netrins as either attractive or repulsive. Netrin-DCC signaling has also been shown to regulate cell death in epithelial cells in vitro, raising the interesting possibility that netrins may also regulate cell death in the developing nervous system. 相似文献
11.
Summary Owing to a new transplantation technique, we have been able to study the sensory projections of homologous and heterologous appendages grafted to the same abdominal site inD. melanogaster. Axons from homologous transplants exhibit similar terminal patterns, whereas those from heterologous transplants do not. It is suggested that ectopic sensory axons specifically recognized central areas and pathways occupied by axons from homologous appendages. 相似文献
12.
Leung JY Bennett WR Herbert RP West AK Lee PR Wake H Fields RD Chuah MI Chung RS 《Cellular and molecular life sciences : CMLS》2012,69(5):809-817
Prior studies have reported that metallothionein I/II (MT) promote regenerative axonal sprouting and neurite elongation of
a variety of central nervous system neurons after injury. In this study, we evaluated whether MT is capable of modulating
regenerative axon outgrowth of neurons from the peripheral nervous system. The effect of MT was firstly investigated in dorsal
root ganglion (DRG) explants, where axons were scratch-injured in the presence or absence of exogenous MT. The application
of MT led to a significant increase in regenerative sprouting of neurons 16 h after injury. We show that the pro-regenerative
effect of MT involves an interaction with the low-density lipoprotein receptor megalin, which could be blocked using the competitive
antagonist RAP. Pre-treatment with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 also completely abrogated
the effect of exogenous MT in promoting axonal outgrowth. Interestingly, we only observed megalin expression in neuronal soma
and not axons in the DRG explants. To investigate this matter, an in vitro injury model was established using Campenot chambers,
which allowed the application of MT selectively into either the axonal or cell body compartments after scratch injury was
performed to axons. At 16 h after injury, regenerating axons were significantly longer only when exogenous MT was applied
solely to the soma compartment, in accordance with the localized expression of megalin in neuronal cell bodies. This study
provides a clear indication that MT promotes axonal regeneration of DRG neurons, via a megalin- and MAPK-dependent mechanism. 相似文献
13.
Wiring of vascular and neural networks requires precise guidance of growing blood vessels and axons, respectively, to reach
their targets during development. Both of the processes share common molecular signaling pathways. Transient receptor potential
canonical (TRPC) channels are calcium-permeable cation channels and gated via receptor- or store-operated mechanisms. Recent
studies have revealed the requirement of TRPC channels in mediating guidance cue-induced calcium influx and their essential
roles in regulating axon navigation and angiogenesis. Dissecting TRPC functions in these physiological processes may provide
therapeutic implications for suppressing pathological angiogenesis and improving nerve regeneration. 相似文献
14.
The mammalian olfactory system has the unique property in the permanent turnover of the olfactory sensory neurons under normal
conditions and following injury. This implies that the topographical map of the epithelium-to-bulb connections generated during
ontogenesis has to be maintained despite neuron renewal in order to insure olfactory information processing. One way to investigate
this issue has been to disrupt the peripheral connections and analyze how neural connections may be reestablished as well
as how animals may perform in olfactory-mediated tasks. This review surveys the main data pertaining to both morphological
and functional recoveries taking place in the peripheral olfactory system following olfactory bulb deafferentation. Conclusions
from these studies are enlightened by recent data from molecular biology. 相似文献
15.
Windus LC Chehrehasa F Lineburg KE Claxton C Mackay-Sim A Key B St John JA 《Cellular and molecular life sciences : CMLS》2011,68(19):3233-3247
Axons of primary olfactory neurons are intimately associated with olfactory ensheathing cells (OECs) from the olfactory epithelium until the final targeting of axons within the olfactory bulb. However, little is understood about the nature and role of interactions between OECs and axons during development of the olfactory nerve pathway. We have used high resolution time-lapse microscopy to examine the growth and interactions of olfactory axons and OECs in vitro. Transgenic mice expressing fluorescent reporters in primary olfactory axons (OMP-ZsGreen) and ensheathing cells (S100ß-DsRed) enabled us to selectively analyse these cell types in explants of olfactory epithelium. We reveal here that rather than providing only a permissive substrate for axon growth, OECs play an active role in modulating the growth of pioneer olfactory axons. We show that the interactions between OECs and axons were dependent on lamellipodial waves on the shaft of OEC processes. The motility of OECs was mediated by GDNF, which stimulated cell migration and increased the apparent motility of the axons, whereas loss of OECs via laser ablation of the cells inhibited olfactory axon outgrowth. These results demonstrate that the migration of OECs strongly regulates the motility of axons and that stimulation of OEC motility enhances axon extension and growth cone activity. 相似文献
16.
Extracellular matrix and neuronal movement 总被引:1,自引:0,他引:1
P. Liesi 《Cellular and molecular life sciences : CMLS》1990,46(9):900-907
Summary During brain development, both neuronal migration and axon guidance are influenced by extracellular matrix molecules present in the environment of the migrating neuronal cell bodies and nerve fibers. Glial laminin is an extracellular matrix protein which these early brain cells preferentially attach to. Extracellular glycosaminoglycans are suggested to function in restricting neuronal cell bodies and axons from certain brain areas. Since laminin is deposited along the radial glial fibers and along the developing nerve pathways in punctate form, the punctate assemblies may be one of the key factors in routing the developing neurons in vivo. This review discusses the role of laminin in neuronal movement given the present concept of the extracellular matrix molecules and their proposed interactions. 相似文献
17.
Extracellular matrix and neuronal movement 总被引:3,自引:0,他引:3
P Liesi 《Experientia》1990,46(9):900-907
During brain development, both neuronal migration and axon guidance are influenced by extracellular matrix molecules present in the environment of the migrating neuronal cell bodies and nerve fibers. Glial laminin is an extracellular matrix protein which these early brain cells preferentially attach to. Extracellular glycosaminoglycans are suggested to function in restricting neuronal cell bodies and axons from certain brain areas. Since laminin is deposited along the radial glial fibers and along the developing nerve pathways in punctate form, the punctate assemblies may be one of the key factors in routing the developing neurons in vivo. This review discusses the role of laminin in neuronal movement given the present concept of the extracellular matrix molecules and their proposed interactions. 相似文献
18.
Neurotrophins are a family of structurally and functionally related neurotrophic factors which, in mammals, include: nerve
growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NT-3), and NT-4/5. In addition to their canonical role in
promoting neuronal survival, these molecules appear to regulate multiple aspects of the development of the nervous system
in vertebrates, including neuronal differentiation, axon elongation and target innervation, among others. Actions of neurotrophins
and of their receptors in vivo are being analyzed by loss-of-function or gain-of-function experiments in mice. Here, we review
the phenotypes of the primary sensory system in these mutant mouse strains and the different strategies specifically involved
in the regulation of neuronal survival by neurotrophins in this portion of the nervous system.
Received 10 December 2001; received after revision 11 May 2002; accepted 13 May 2002
RID="*"
ID="*"Corresponding author. 相似文献
19.
Olfactory receptors 总被引:1,自引:0,他引:1
Olfaction is an ancient sensory system allowing an organism to detect chemicals in its environment. The first step in odor transduction is mediated by binding odorants to olfactory receptors (ORs) which belong to the heptahelical G-protein-coupled receptor (GPCR) superfamily. Mammalian ORs are disposed in clusters on virtually all chromosomes. They are encoded by the largest multigene family (1000 members) in the genome of mammals and Caenorhabditis elegans, whereas Drosophila contains only 60 genes. Each OR specifically recognizes a set of odorous molecules that share common molecular features. In mammals, signal transduces through the G-protein-dependent signal pathway in the olfactory sensory neurons that synapse ultimately in the glomeruli of the olfactory bulb, and is finally processed in higher brain structures. The expression of a given OR conditions neuron and glomerulus choices. To date, the processes which monitor OR expression and axon wiring have emerged but are not completely elucidated.Received 9 July 2003; reiceived after revision 3 Ocotober 2003; accepted 22 Ocotober 2003 相似文献
20.
Myelin sheaths: glycoproteins involved in their formation,maintenance and degeneration 总被引:8,自引:0,他引:8
Quarles RH 《Cellular and molecular life sciences : CMLS》2002,59(11):1851-1871
Myelin sheaths are formed around axons by extending, biochemically modifying and spiraling plasma membranes of Schwann cells
in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Because glycoproteins are
prominent components of plasma membranes, it is not surprising that they have important roles in the formation, maintenance
and degeneration of myelin sheaths. The emphasis in this review is on four integral membrane glycoproteins. Two of them, protein
zero (P0) and peripheral myelin protein-22 (PMP-22), are components of compact PNS myelin. The other two are preferentially
localized in membranes of sheaths that are distinct from compact myelin. One is the myelin-associated glycoprotein, which
is localized at the inside of sheaths where it functions in glia-axon interactions in both the PNS and CNS. The other is the
myelin-oligodendrocyte glycoprotein, which is preferentially localized on the outside of CNS myelin sheaths and appears to
be an important target antigen in autoimmune demyelinating diseases such as multiple sclerosis.
Received 8 April 2002; received after revision 13 May 2002; accepted 22 May 2002 相似文献