Oligodendrocytes repel axons and cause axonal growth cone collapse

1989 ◽  
Vol 92 (1) ◽  
pp. 93-100 ◽  
Author(s):  
J.W. Fawcett ◽  
J. Rokos ◽  
I. Bakst
Keyword(s):  
Growth Cone ◽  
Dorsal Root ◽  
Axonal Growth ◽  
Time Lapse ◽  
Growth Cones ◽  
Newborn Rats ◽  
Growth Cone Collapse ◽  
Axonal Growth Cone ◽  
Video Studies ◽  
Culture Surface

We have examined the interactions between axons regenerating from dorsal root ganglia (DRGs) derived from newborn rats and oligodendrocytes cultured by three different techniques. Cultures examined after 2 days have a profuse outgrowth of axons from the DRGs, forming a dense mat on the culture surface. However, the axons avoid growing on oligodendrocytes; axons are seen all around these cells, but do not grow over them. We have also performed time-lapse video studies of the interactions between axonal growth cones and oligodendrocytes. Axons grow normally until their growth cone comes into direct contact with an oligodendrocyte, following which the growth cone remains motile for 30–60 min, but without making any progress over the cell. The growth cone then suddenly collapses, and the axon retracts, leaving a thin strand in contact with the cell. After this a new growth cone is usually elaborated and the process repeated. Oligodendrocytes are therefore inhibitory to axonal growth, and this may partially explain the failure of axons to regenerate in the mammalian central nervous system.

scholarly journals Plexin-B1/RhoGEF–mediated RhoA activation involves the receptor tyrosine kinase ErbB-2

2004 ◽  
Vol 165 (6) ◽  
pp. 869-880 ◽  
Author(s):  
Jakub M. Swiercz ◽  
Rohini Kuner ◽  
Stefan Offermanns
Keyword(s):  
Tyrosine Kinase ◽  
Growth Cone ◽  
Receptor Tyrosine Kinase ◽  
Hippocampal Neurons ◽  
Molecular Mechanisms ◽  
Axonal Growth ◽  
Dominant Negative ◽  
Growth Cone Collapse ◽  
Rhoa Activation ◽  
Axonal Growth Cone

Plexins are widely expressed transmembrane proteins that mediate the effects of semaphorins. The molecular mechanisms of plexin-mediated signal transduction are still rather unclear. Plexin-B1 has recently been shown to mediate activation of RhoA through a stable interaction with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. However, it is unclear how the activity of plexin-B1 and its downstream effectors is regulated by its ligand Sema4D. Here, we show that plexin-B family members stably associate with the receptor tyrosine kinase ErbB-2. Binding of Sema4D to plexin-B1 stimulates the intrinsic tyrosine kinase activity of ErbB-2, resulting in the phosphorylation of both plexin-B1 and ErbB-2. A dominant-negative form of ErbB-2 blocks Sema4D-induced RhoA activation as well as axonal growth cone collapse in primary hippocampal neurons. Our data indicate that ErbB-2 is an important component of the plexin-B receptor system and that ErbB-2–mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation, which underlies cellular phenomena downstream of plexin-B1, including axonal growth cone collapse.

scholarly journals Unique Responses of Differentiating Neuronal Growth Cones to Inhibitory Cues Presented by Oligodendrocytes

1998 ◽  
Vol 142 (1) ◽  
pp. 191-202 ◽  
Author(s):  
A. Shibata ◽  
M.V. Wright ◽  
S. David ◽  
L. McKerracher ◽  
P.E. Braun ◽  
...  
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Dendritic Growth ◽  
System Development ◽  
Axonal Growth ◽  
Growth Cones ◽  
Nervous System Development ◽  
Environmental Cues ◽  
Growth Cone Collapse ◽  
Neuronal Growth Cones

During central nervous system development, neurons differentiate distinct axonal and dendritic processes whose outgrowth is influenced by environmental cues. Given the known intrinsic differences between axons and dendrites and that little is known about the response of dendrites to inhibitory cues, we tested the hypothesis that outgrowth of differentiating axons and dendrites of hippocampal neurons is differentially influenced by inhibitory environmental cues. A sensitive growth cone behavior assay was used to assess responses of differentiating axonal and dendritic growth cones to oligodendrocytes and oligodendrocyte- derived, myelin-associated glycoprotein (MAG). We report that >90% of axonal growth cones collapsed after contact with oligodendrocytes. None of the encounters between differentiating, MAP-2 positive dendritic growth cones and oligodendrocytes resulted in growth cone collapse. The insensitivity of differentiating dendritic growth cones appears to be acquired since they develop from minor processes whose growth cones are inhibited (nearly 70% collapse) by contact with oligodendrocytes. Recombinant MAG(rMAG)-coated beads caused collapse of 72% of axonal growth cones but only 29% of differentiating dendritic growth cones. Unlike their response to contact with oligodendrocytes, few growth cones of minor processes were inhibited by rMAG-coated beads (20% collapsed). These results reveal the capability of differentiating growth cones of the same neuron to partition the complex molecular terrain they navigate by generating unique responses to particular inhibitory environmental cues.

scholarly journals hnRNP Q Regulates Internal Ribosome Entry Site-Mediated fmr1 Translation in Neurons

2018 ◽  
Vol 39 (4) ◽  
Author(s):  
Jung-Hyun Choi ◽  
Sung-Hoon Kim ◽  
Young-Hun Jeong ◽  
Sung Wook Kim ◽  
Kyung-Tai Min ◽  
...  
Keyword(s):  
Growth Cone ◽  
Internal Ribosome Entry Site ◽  
Rna Binding ◽  
Regulatory Mechanism ◽  
Fragile X ◽  
Axonal Growth ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Growth Cone Collapse ◽  
Axonal Growth Cone

ABSTRACT Fragile X syndrome (FXS) caused by loss of fragile X mental retardation protein (FMRP), is the most common cause of inherited intellectual disability. Numerous studies show that FMRP is an RNA binding protein that regulates translation of its binding targets and plays key roles in neuronal functions. However, the regulatory mechanism for FMRP expression is incompletely understood. Conflicting results regarding internal ribosome entry site (IRES)-mediated fmr1 translation have been reported. Here, we unambiguously demonstrate that the fmr1 gene, which encodes FMRP, exploits both IRES-mediated translation and canonical cap-dependent translation. Furthermore, we find that heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) acts as an IRES-transacting factor (ITAF) for IRES-mediated fmr1 translation in neurons. We also show that semaphorin 3A (Sema3A)-induced axonal growth cone collapse is due to upregulation of hnRNP Q and subsequent IRES-mediated expression of FMRP. These data elucidate the regulatory mechanism of FMRP expression and its role in axonal growth cone collapse.

scholarly journals Rapid changes in the distribution of GAP-43 correlate with the expression of neuronal polarity during normal development and under experimental conditions.

1990 ◽  
Vol 110 (4) ◽  
pp. 1319-1331 ◽  
Author(s):  
K Goslin ◽  
G Banker
Keyword(s):  
Growth Cone ◽  
Hippocampal Neurons ◽  
Time Course ◽  
Axonal Growth ◽  
Growth Cones ◽  
Growth Characteristics ◽  
Neuronal Polarity ◽  
Experimental Conditions ◽  
Axonal Growth Cone ◽  
Axonal Transection

Hippocampal neurons growing in culture initially extend several, short minor processes that have the potential to become either axons or dendrites. The first expression of polarity occurs when one of these minor processes begins to elongate rapidly, becoming the axon. Before axonal outgrowth, the growth-associated protein GAP-43 is distributed equally among the growth cones of the minor processes; it is preferentially concentrated in the axonal growth cone once polarity has been established (Goslin, K., D. Schreyer, J. Skene, and G. Banker. 1990. J. Neurosci. 10:588-602). To determine when the selective segregation of GAP-43 begins, we followed individual cells by video microscopy, fixed them as soon as the axon could be distinguished, and localized GAP-43 by immunofluorescence microscopy. Individual minor processes acquired axonal growth characteristics within a period of 30-60 min, and GAP-43 became selectively concentrated to the growth cones of these processes with an equally rapid time course. We also examined changes in the distribution of GAP-43 after transection of the axon. After an axonal transection that is distant from the soma, neuronal polarity is maintained, and the original axon begins to regrow almost immediately. In such cases, GAP-43 became selectively concentrated in the new axonal growth cone within 12-30 min. In contrast, when the axon is transected close to the soma, polarity is lost; the original axon rarely regrows, and there is a significant delay before a new axon emerges. Under these circumstances, GAP-43 accumulated in the new growth cone much more slowly, suggesting that its ongoing selective routing to the axon had been disrupted by the transection. These results demonstrate that the selective segregation of GAP-43 to the growth cone of a single process is closely correlated with the acquisition of axonal growth characteristics and, hence, with the expression of polarity.

scholarly journals Growth Cone Collapse through Coincident Loss of Actin Bundles and Leading Edge Actin without Actin Depolymerization

2001 ◽  
Vol 153 (5) ◽  
pp. 1071-1084 ◽  
Author(s):  
Feng-quan Zhou ◽  
Christopher S. Cohan
Keyword(s):  
Growth Cone ◽  
Kinase Inhibitor ◽  
Leading Edge ◽  
Time Lapse ◽  
Growth Cones ◽  
Filamentous Actin ◽  
Actin Bundle ◽  
Actin Bundles ◽  
Growth Cone Collapse ◽  
Substrate Adhesion

Repulsive guidance cues can either collapse the whole growth cone to arrest neurite outgrowth or cause asymmetric collapse leading to growth cone turning. How signals from repulsive cues are translated by growth cones into this morphological change through rearranging the cytoskeleton is unclear. We examined three factors that are able to induce the collapse of extending Helisoma growth cones in conditioned medium, including serotonin, myosin light chain kinase inhibitor, and phorbol ester. To study the cytoskeletal events contributing to collapse, we cultured Helisoma growth cones on polylysine in which lamellipodial collapse was prevented by substrate adhesion. We found that all three factors that induced collapse of extending growth cones also caused actin bundle loss in polylysine-attached growth cones without loss of actin meshwork. In addition, actin bundle loss correlated with specific filamentous actin redistribution away from the leading edge that is characteristic of repulsive factors. Finally, we provide direct evidence using time-lapse studies of extending growth cones that actin bundle loss paralleled collapse. Taken together, these results suggest that actin bundles could be a common cytoskeletal target of various collapsing factors, which may use different signaling pathways that converge to induce growth cone collapse.

Direct Neurotoxicity of Tetracaine on Growth Cones and Neurites of Growing Neurons In Vitro 

2001 ◽  
Vol 95 (3) ◽  
pp. 726-733 ◽  
Author(s):  
Shigeru Saito ◽  
Inas Radwan ◽  
Hideaki Obata ◽  
Kenichiro Takahashi ◽  
Fumio Goto
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Dorsal Root Ganglion ◽  
Growth Cone ◽  
Local Anesthetics ◽  
Dorsal Root ◽  
Sympathetic Ganglion ◽  
Growth Cones ◽  
Growth Cone Collapse ◽  
Neuronal Tissues

Background Local anesthetics have direct neurotoxicity on neurons. However, precise morphologic changes induced by the direct application of local anesthetics to neurons have not yet been fully understood. Also, despite the fact that local anesthetics are sometimes applied to the sites where peripheral nerves may be regenerating after injury, the effects of local anesthetics on growing or regenerating neurons have never been studied. Methods Three different neuronal tissues (dorsal root ganglion, retinal ganglion cell layer, and sympathetic ganglion chain) were isolated from an age-matched chick embryo and cultured for 20 h. Effects of tetracaine were examined microscopically and by a quantitative morphologic assay, growth cone collapse assay. Results Tetracaine induced growth cone collapse and neurite destruction. Three neuronal tissues showed significantly different dose-response, both at 60 min and at 24 h after the application of tetracaine (P < 0.01). The ED50 values (mean +/- SD) at 60 min were 1.53+/-1.05 mM in dorsal root ganglion, 0.15+/-0.05 mM in retinal, and 0.06+/-0.02 mM in sympathetic ganglion chain cultures. The ED50 values at 24 h were 0.43+/-0.15 mM in dorsal root ganglion, 0.07+/-0.03 mM in retinal, and 0.02+/-0.01 mM in sympathetic ganglion chain cultures. Concentration of nerve growth factor in the culture media did not influence the ED50 values. The growth cone collapsing effect was partially reversible in dorsal root ganglion and retinal neurons. However, in the sympathetic ganglion culture, no reversibility was observed after exposure to 1 mM tetracaine for 10 or for 60 min. Bupivacaine had similar neurotoxicity to the three types of growing neurons. (The ED50 values at 60 min were 2.32+/-0.50 mM in dorsal root ganglion, 0.96+/-0.16 mM in retinal, and 0.18+/-0.05 mM in sympathetic ganglion chain cultures. The ED50 values at 24 h were 0.34+/-0.09 mM in dorsal root ganglion, 0.21+/-0.06 mM in retinal, and 0.45+/-0.10 mM in sympathetic ganglion chain cultures.) Conclusions Short-term exposure to tetracaine produced irreversible changes in growing neurons. Growth cones were quickly affected, and neurites degenerated subsequently. Sensitivity varied with neuronal type and was not influenced by the concentration of nerve growth factor. Because a similar phenomenon was observed after exposure to bupivacaine, the toxicity to growing neurons may not be unique to tetracaine.

Sign in / Sign up

Export Citation Format

Share Document