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Axonal ion channel dysfunction in amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) it is not known how or why the motor neurons die, but a clue is provided by observations that the dying cells discharge spontaneously, producing muscle fasciculations. The fasciculations can arise either proximally or distally in the motor unit, suggesting a widespread disturbance of membrane excitability. To test for this, we applied the technique of threshold electrotonus to ulnar motor axons at the wrist, comparing the responses to 100 ms polarizing currents in 11 ALS patients with those from 15 normal controls, six patients with benign fasciculations, 19 with lower motor neuron disorders and six with upper motor neuron disorders. We found that the motor axons of ALS patients, unlike those in the neurological control groups, responded abnormally to subthreshold depolarizing currents, becoming either more (seven cases) or much less excitable (four cases) than normal. Both types of abnormality could be reproduced in rat nerves in vitro, and in a computer model of human motor axons, by reducing voltage dependent potassium conductances. When sufficient potassium channels were blocked, the model axon became unstable and depolarized regeneratively, resulting in an abrupt fall in excitability. We conclude that the fasciculations in ALS are caused by an imbalance between functional sodium and potassium channels, and we propose that this ion channel dysfunction could also be responsible for the motor neuron degeneration in this disease.

Adult↗

Phenytoin reduces suxamethonium-induced myalgia.

A prospective, randomised trial was undertaken in 60 healthy adults to determine the efficacy of intravenously administered phenytoin in doses of 5 mg.kg-1 for the prevention of suxamethonium-induced fasciculations, a rise in serum K+ and myalgia. This was compared with tubocurarine pretreatment and no pretreatment (control group). Phenytoin pretreatment significantly reduced myalgia from 45% (nine patients) in the control group to 10% (two patients) (p less than 0.05). It also decreased the duration and mean intensity of fasciculations. Incidentally, phenytoin was also found to decrease significantly mean serum Na+ levels (p less than 0.001) both at 5 and 20 min after administration. Tubocurarine pretreatment (3 mg) resulted in a significant decrease in fasciculations, but myalgia, which occurred in five patients, remained the same. No significant correlation was found between muscle fasciculations, postoperative myalgia and K+ changes, but patients with myalgia had a significant decrease in mean serum Na+ levels at 5 and 20 min after suxamethonium (p less than 0.01).

Adult↗

[A patient with motor neuron syndrome clinically similar to amyotrophic lateral sclerosis, presenting spontaneous recovery].

We report a patient with motor neuron syndrome similar to amyotrophic lateral sclerosis (ALS) and with spontaneous recovery. At the age 40, the woman developed progressive muscular weakness, atrophy and fasciculation in extremities. She also noted a dyspnea, tongue atrophy and dysphagia. A neurological examination 6 months after onset revealed i) a tongue atrophy and fasciculation, ii) diffuse muscule weakness and atrophy in face, neck and extremities, and iii) marked hyperreflexia in the four limbs and bilateral Babinski reflex, but iv) neither sensory disturbance nor ophthalmoplegia. Electromyogram (EMG) detected such denervation potentials as fibrillation potentials, fasciculation potentials, positive sharp waves and polyphasic or giant MUPs diffusely in the limb muscles. Peripheral nerve conduction study detected neither conduction block nor delay. Thus, she was diagnosed as suffering from ALS. However, since approximate 1 year after onset, her muscle weakness has gradually been getting better. Simultaneously, the dyspnea and dysphagia gradually improved. Two years after onset, an EMG examination detected chronic denervation potentials in the left musculus sternocleidomastoideus and a few on-going denervation potentials in the left musculus extensor carpi radialis, but no denervation potentials in other limb muscles. Fasciculation potentials were found in tongue muscles. Thus, the present case was thought to have a reversible motor neuron syndrome clinically quite similar to ALS. A mild increase in IgE (346 U/ml) and a low-titer IgM-class anti-GM1 antibody were found in her serum though its pathological significance was uncertain. Any immunological aberrance may account for the pathogenesis. It should be noted that clinically diagnosed cases of ALS may rarely recover spontaneously.

Adult↗

[The study of pretreatment with diphenylhydantoin or D-tubocurarine on succinylcholine-induced adverse effects].

Intravenous succinylcholine (SCh) is widely used as a muscle relaxant but it is often associated with adverse effects, including muscle fasciculations, postoperative myalgia, elevated serum potassium (K+) and creatine phosphokinase (CPK), etc. The present study was undertaken to evaluate the effects of pretreatment with Diphenylhydantoin (DPH) or d-Tubocurarine (d-TC) on SCh-induced adverse effects. 54 ASA I-II adult patients were randomly divided into 3 groups of 18 patients each. Four min before injection of SCh, group A received 1 ml of normal saline as a control group, group B DPH 2.5 mg kg-1 and group C d-TC 50 micrograms kg-1. Anesthesia was induced with thiopentone 3-4 mg kg-1 and then SCh was given to facilitate tracheal intubation. Anesthesia was maintained with isoflurane and nitrous oxide in oxygen. Muscle fasciculations, postoperative 24 hours myalgia, intubating conditions and levels of serum K+, CPK and DPH were recorded in every patient. All data were analyzed with Chi-Square and ANOVA tests. DPH and d-TC significantly decreased the incidence of fasciculations, whereas there were no differences regarding intubating condition, post-operative myalgia, and serum K+ among three groups. DPH concentration was 8.49 +/- 1.55 micrograms ml-1. Serum CPK was increased postoperatively in three groups. Pretreatment with DPH 2.5 mg kg-1 or d-TC 50 micrograms kg-1 effectively decreased SCh-induced fasciculations and did not affect intubating condition facilitated with SCh 1.5 mg kg-1. Nevertheless, these pretreatment did not improve postoperative myalgia and decrease serum CPK.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Glia are a unique substrate for the in vitro growth of central nervous system neurons.

We have examined the consequences of surface interactions with glial and nonglial cells on the in vitro growth of CNS neurons. When cerebellar or spinal cord cells were plated onto monolayers highly enriched in cortical astrocytes or sciatic nerve Schwann cells, neurons generally grew as single cells and showed relatively little tendency to aggregate. Similarly, neurites showed little tendency to fasciculate. In contrast, when plated onto fibroblast, heart muscle-fibroblast, or astrocyte-free meningeal monolayers, neurons rapidly aggregated, and neurite outgrowth was primarily in large fascicles. There were no glia detectable in the majority of aggregates or fascicles, suggesting that aggregation and fasciculation were due to interactions between neurons. Neurite outgrowth over 24 hr was also greater on astrocytes than on nonglia. Whether or not aggregation and fasciculation occurred was due to surface properties of the glial and nonglial cells. When neurons were added to astrocyte and nonglial monolayers growing in medium conditioned by a large excess of co-cultured nonglia or astrocytes, respectively, the pattern of neuronal growth was determined by the type of monolayer with which the neurons were in contact. Moreover, the initial growth of neurons on heat-killed astrocytes was indistinguishable from growth on living astrocytes. The pattern of neuronal growth on these different monolayers suggests that neurons are more adherent to glia than to other neurons but are more adherent to other neurons than to nonglia. Such an adherence hierarchy could explain the consistent finding of an apposition of neurons to glial surfaces during neuronal migration and axon outgrowth. Our findings also suggest that the interaction of axons with the non-neuronal milieu through which they grow may play an important role in regulating fasciculation, a process which has generally been treated as due primarily to axon-axon interactions.

Animals↗

[Study on the intraneural topography of the brachial plexus].

An accurate intraneural topography of the nerve fascicules in the brachial plexus provides a correct diagnosis and proper treatment of brachial nerve injuries. Four specimens of the branchial plexus were harvested from human cadavers by careful dissection and serially cross-sectioned from the nerve root level to the peripheral nerve. A spatial relationship between each nerve fascicule was observed and traced proximo-distally with a stereoscopic microscope. The main results and conclusions are as follows: 1. Four types of normal variation were identified in the composing elements of the brachial plexus. It is special interest to note the one in which both the fifth and sixth cervical nerve roots are composed of the dorsal scapular nerve. The existence of normal variations should be taken into account when determining the level and degree of branchial plexus injuries. 2. The nerve fascicules composing each peripheral nerve are most easily discerned at the cord level of the branchial plexus where there are no definite fiber exchanges between those nerve fascicules. These results would indicate that reconstructive nerve operations can be done successfully at the cord level or, at most, at the division level.

Brachial Plexus↗

Train-of-four fade of non depolarizing muscle relaxants: an insight into the mechanism of precurarization.

This study was carried out to assess the prejunctional effect of non depolarizing muscle relaxants during the onset of neuromuscular blockade using the train-of-four ratio (TR). The prejunctional effect was compared with previous results concerning the ability of the relaxants to prevent suxamethonium-induced fasciculations. Fifty-three adult patients were relaxed with small incremental doses of either alcuronium (0.03 mg.kg-1), atracurium (0.04 mg.kg-1), pancuronium (0.01 mg.kg-1), d-tubocurarine (0.05 mg.kg-1) or vecuronium (0.01 mg.kg-1) during anaesthesia with thiopentone, fentanyl and nitrous oxide in oxygen. The muscle relaxant was given after recovery from an initial suxamethonium blockade needed for tracheal intubation. The evoked integrated EMG response to supramaximal train-of-four (2 Hz) stimulation was recorded every 20 s. TR % was calculated at different first twitch (T1) levels during the onset of neuromuscular blockade. Significant changes occurred at the 100% and 90% T1 levels, alcuronium having the lowest mean TR values. Atracurium, pancuronium and vecuronium gave similar TR values. Results with d-tubocurarine placed it between alcuronium and the others. These train-of-four ratio results were compared with the ability of non depolarizing muscle relaxants to prevent fasciculations. In conclusion, the stronger the train-of-four fade, the greater was the ability of the relaxant to prevent suxamethonium-induced fasciculations. This supports the theory that the blockade of prejunctional cholinergic receptors is the mechanism of action of precurarization.

Adolescent↗

Prevalence of denervation in paraspinal and foot intrinsic musculature.

OBJECTIVE: The primary purpose of this investigation was to determine the prevalence of abnormal spontaneous activity (positive sharp waves (PSWs) and fibrillation potentials (FPs)) in selected lumbosacral paraspinal and foot intrinsic muscles in an asymptomatic healthy population. DESIGN: This was a prospective assessment of 50 individuals without history or physical findings suggestive of peripheral neuromuscular disease whereby a monopolar needle electrode was located in the unilateral L4 and L5 paraspinal as well as abductor hallucis and extensor digitorum brevis muscles. These muscles were extensively evaluated for the presence of PSWs, FPs, and fasciculation potentials. RESULTS: Ten subjects per decade from 20-59 yr and ten subjects from 60-80 yr comprised the 50 participants (28 women), resulting in a mean age of 45+/-15.9 (range, 20-76) yr. A single individual (prevalence, 2%) demonstrated fibrillation potentials in the extensor digitorum brevis, and FPs and PSWs were detected in two subjects' (4% prevalence) L4/L5 paraspinal muscles. Ninety-four percent of the subjects had fasciculation potentials in the abductor hallucis, whereas 60% had these waveforms in the extensor digitorum brevis. Only 6% of subjects had fasciculation potentials in the L4 but not L5 paraspinal muscles. All subjects demonstrated both prototypical and "atypical" appearing endplate spikes in all of the muscles examined. CONCLUSIONS: We failed to confirm the previously reported prevalence of FPs and PSWs in both the paraspinal and foot intrinsic musculature. Atypical appearing endplate spikes, however, display configurations similar to FPs and PSWs and were present in all subjects. Failure to pay close attention to the discharge rate and rhythm of endplate spikes can lead to misinterpreting these waveforms as FPs and PSWs. It is likely that the previously reported high prevalence of spontaneous activity in healthy persons resulted from not fully appreciating the similarity between innervated and denervated spontaneous single muscle fiber discharge configurations.

Action Potentials↗

Optimal time interval between pretreatment with alcuronium and suxamethonium during anaesthetic induction.

Alcuronium 0.03 mg/kg was studied in a double-blind randomized fashion as a pretreatment before suxamethonium using different time intervals between the administration of the drugs in 78 patients (ASA I-II) undergoing otolaryngological surgery. Alcuronium was given 1, 2 or 3 min before suxamethonium 1.5 mg/kg. The control group received saline as a pretreatment and suxamethonium 1 mg/kg. Anaesthesia was induced with thiopental 5.5 mg/kg over 60 s. Muscle fasciculations, intubating conditions, cardiovascular responses to endotracheal intubation and duration of neuromuscular block were assessed. Muscle fasciculations were statistically and similarly inhibited (P less than 0.01) at all time intervals between alcuronium and suxamethonium. Intubating conditions were worse (P less than 0.05) in the 3-min group than in the other groups. Cardiovascular responses to endotracheal intubation were similar in all groups. The neuromuscular block after suxamethonium was significantly shorter (P less than 0.05) in the 2- and 3-min groups than in the other groups. In conclusion, from the clinical point of view the 1-min time interval between alcuronium and suxamethonium is optimal since muscle fasciculations are inhibited and intubating conditions are satisfactory.

Adult↗

[Abnormal hyperexcitability in ALS].

The defect of neuromuscular transmission is one of the important signs in ALS. The amplitude of a single motor unit potential from patients with ALS often decrease during tonic voluntary contraction. This phenomenon is closely correlated with fatigue seen in the patient. Overfunctioning of Ach release in the nerve terminal might cause the failure of neuromuscular transmission in ALS. Fasciculations is an another characteristic sign and considered mainly to be peripheral axons in origin. It is postulated that the dysfunction of potassium channel in ALS axons makes the hyperexcitability of the axon membrane, causing fasciculations. Magnetic cortical stimulation sometimes evokes the same potentials as fasciculations, implying the hyperexcitability might be present also in spinal motoneurons or even in pyramidal neurons in ALS. All of these findings lead to the hypothesis that hyperexcitability or overactivity of central and peripheral motoneurons is an essential feature in ALS.

Amyotrophic Lateral Sclerosis↗

Effectiveness of atracurium in preventing succinylcholine myalgia.

A comparison was made of the incidence of postoperative myalgia (POM) and fasciculations when atracurium (ATR) or d-Tubocurarine (DTC) was given prior to succinylcholine (SDC) for facilitation of tracheal intubation. The subjects were 44 ASA physical status I or II outpatient females undergoing laparoscopy. They were assigned to one of three groups: Group 1 received 0.025 mg/kg ATR; Group 2 received 0.05 mg/kg DTC, and Group 3 received saline (NS). Thiopental was administered one minute and 45 seconds after pretreatment. Three minutes after pretreatment, SDC 1.5 mg/kg was given, and fasciculations were recorded on a scale of 0-3. The patients were questioned one and three days postoperatively about POM and their responses recorded using a scale of 0-3. Fasciculations occurred in 79% of patients given saline, in 46% of those receiving ATR and in 12% of those given DTC. Eighty-five percent of ATR patients were free of POM on postoperative day one. The corresponding figures for DTC and NS were 59% and 43%, respectively. The difference between ATR and NS achieved statistical significance, leading to the conclusion that DTC is a better defasciculant than ATR. DTC was, however, not significantly better than NS in the prevention of POM. Findings suggest that ATR may be the drug of choice for the prevention of POM.

Adolescent↗

Comparison of atracurium and d-tubocurarine for prevention of succinylcholine myalgia.

We compared the incidence of postoperative myalgia (POM) and fasciculations when atracurium (ATR) or d-tubocurarine (DTC) was given prior to succinylcholine (SDC) for tracheal intubation in 44 ASA class I or II outpatient females undergoing laparoscopy. The subjects were assigned to one of three groups: group 1 received 0.025 mg/kg ATR; group 2 received 0.05 mg/kg DTC; and group 3 received saline (NS), all in a double-blind manner. Thiopental was administered 1 min and 45 sec after pretreatment in doses adequate to allow control of ventilation. Three minutes after pretreatment, SDC 1.5 mg/kg was given, and fasciculations were recorded on a scale of 0-3. All patients were questioned 1 and 3 days postoperatively about POM, using a scale of 0-3. Fasciculations occurred in 79% of patients given saline, in 46% of those receiving ATR, and in 12% of those given DTC. Eighty-five percent of ATR patients were free of POM on postoperative day 1. The corresponding figures for DTC and NS were 59% and 43%, respectively. Only the difference between ATR and NS achieved statistical significance. On the third postoperative day, POM was rare and there were no significant differences among the groups. We conclude that DTC is a better defasciculant than ATR. DTC was, however, not significantly better than NS in the prevention of POM. The findings suggest that ATR may be the drug choice for the prevention of POM.

Adolescent↗

Intravenous flunitrazepam in the prevention of the side effects of succinylcholine.

Muscular fasciculations, plasma potassium levels and postoperative muscle pains following succinylcholine injection were studied in 64 patients who had been given either dilute flunitrazepam or sodium thiopental to induce anesthesia. In the 32 patients with flunitrazepam-induced anesthesia, muscle fasciculations were present in only 8 and postoperative muscle pains in 4, while none of the patients had elevated plasma potassium. In the thiopental group, muscle fasciculations and postoperative muscle pains were present in 28 and 22 of the other 32 patients, respectively, while all had significantly elevated plasma potassium levels. Flunitrazepam appears to be a useful alternative anesthesia-induction agent that prevents some of the side effects of succinylcholine without reducing its efficiency.

Adolescent↗

N-acetyl-lactosamine in the rat olfactory system: expression and potential role in neurite growth.

Primary sensory olfactory neurons exhibit a mosaic topographical projection from the olfactory neuroepithelium in the nasal cavity to the olfactory bulb formation of the telencephalon. Axons from primary neurons that are widely scattered in the epithelium terminate in discrete regions of the olfactory bulb. It has been hypothesised that carbohydrates present on the surface of primary olfactory axons mediate selective fasciculation and the formation of the topographical pathway. We examined the expression of the disaccharide N-acetyl-lactosamine in both the developing and the adult rat olfactory system. N-acetyl-lactosamine was expressed by all primary sensory olfactory neurons and by their terminations in the olfactory bulb throughout embryonic development and early postnatal life. In adults, N-acetyl-lactosamine was restricted to a subpopulation of primary sensory olfactory neurons that were dispersed throughout the neuroepithelium but that projected predominantly to the ventrolateral and ventromedial surfaces of the olfactory bulb. The axons of these neurons sort out in the outer layer of the bulb and preferentially self-fasciculate to form distinct axon bundles that terminate within select glomeruli. The role of N-acetyl-lactosamine in axon growth was tested by culturing primary sensory olfactory neurons on substrate-bound carbohydrates. Olfactory neuroepithelium cultures from both embryonic and postnatal rats revealed that substrate-bound N-acetyl-lactosamine was a strong and specific neurite growth-promoting agent. These data suggest that, during development of the olfactory projection, N-acetyl-lactosamine, which is present on all olfactory axons, acts as a nonselective permissive substrate for axon growth. In adults, however, the restricted distribution of N-acetyl-lactosamine on a subpopulation of axons may facilitate sorting out and self-fasciculation, which is necessary for preserving the mosaic nature of the olfactory pathway in this highly plastic region of the nervous system. These results support the hypothesis that cell surface carbohydrates are involved in axon growth in the olfactory system.

Amino Sugars↗

Expression of extracellular matrix molecules and cell surface molecules in the olfactory nerve pathway during early development.

The spatial and temporal expression patterns of several extracellular matrix molecules--laminin and fibronectin and cell surface molecules, neural cell adhesion molecule (NCAM), L1, tenascin, chondroitin sulfate proteoglycan, and peanut agglutinin (PNA) binding sites--were investigated during early olfactory nerve development. NCAM and L1 have similar patterns: They are expressed in the olfactory nerve and on the olfactory receptor neurons (ORNs) commencing with the earliest olfactory axon outgrowth (E12-E15). Their expression patterns suggest that both NCAM and L1 are associated with extension and fasciculation of olfactory axons. A comparison of L1 and olfactory marker protein suggests that L1 is expressed predominantly on immature ORNs. Laminin has an unique punctate staining pattern in the developing olfactory pathway as early as E12. These laminin puncta might play a role in olfactory neurite outgrowth and guidance. At E14, when pioneer olfactory axons enter the brain, the laminin-positive meninges on the surface of the olfactory bulb primordium break down but remain intact in the rest of the telencephalon. This suggests a functional interaction between the olfactory axons and the glial-pial barrier. Fibronectin staining is diffuse throughout the cranial mesenchyme but is absent from the olfactory nerve pathway. No specific patterns of tenascin or chondroitin sulfate, were observed during early olfactory development. PNA binding sites were associated with olfactory axon fasciculation. The expression of several extracellular matrix molecules and cell surface molecules is spatially and temporally regulated in the developing olfactory system. These molecules, thus, may play functional roles in olfactory axon outgrowth, fasciculation, and/or guidance.

Animals↗

p59fyn and pp60c-src modulate axonal guidance in the developing mouse olfactory pathway.

The Src-family tyrosine kinases p59fyn and pp60c-src are localized on axons of the mouse olfactory nerve during the initial stages of axonal growth, but their functional roles remain to be defined. To study the role of these kinases, we analyzed the trajectory of the olfactory nerve in E11.5 homozygous null mutant mice lacking single src or fyn gens and double mutants lacking both genes. Primary olfactory axons of single and double mutants exited the olfactory epithelium and projected toward the telencephalon, but displayed differences in fasciculation. The fyn-minus olfactory nerve had significantly more fascicles than than src-minus nerve. Most strikingly, the primary olfactory nerve of src/fyn double mutants showed the greatest degree of defasciculation. These defects, identified by NCAM labeling, were not due to apparent changes in the size of the olfactory epithelium. With the exception of the src-minus mice, which had fever fascicles than the wild type, no obvious differences were observed in coalescence of vomeronasal axons from mutant mice. The mesenchyme of the double and single mutants exhibited only subtle changes in laminin and fibronectin staining, indicating that the adhesive environment of the mesenchyme may contribute in part to defects in fasciculation. The results suggest that signaling pathways mediated by p59fyn and pp60c-src contribute to the appropriate fasciculation of axons in the nascent olfactory system, and comprise partially compensatory mechanisms for axonal adhesion and guidance.

Animals↗

Expression of surface glycoproteins early in leech neural development.

Cell migration and axon growth during neural development rely upon cell-cell and cell-matrix interactions mediated by surface glycoproteins. The surface glycoprotein recognized on leech neurons by monoclonal antibody Lan3-2 has previously been implicated in the process of axon fasciculation during regeneration in adults. In adult leeches, Lan3-2 binds to a carbohydrate epitope of a 130 kD protein. The present study demonstrates that in embryos the antibody binds to the same carbohydrate epitope of glycoproteins with molecular weights of 130 kD and higher. As a first step in evaluating a possible role of the Lan3-2 glycoprotein or the cells that express it during neural development, we determined its distribution in the developing nervous system of the leech Hirudo medicinalis. In embryos, Lan3-2 epitope is expressed on fasciculated sensory afferents and it appears on the cell bodies before neurite outgrowth. The sensory fibers appear rostrally by embryonic day 10, less than halfway through development. Earlier, by 7 days of development at 20 degrees C, Lan3-2 binds to previously undocumented cell types: (1) cells appearing along the embryonic midline and (2) a cluster of cells located at the rostral edge of the germinal plate. These cells only transiently express this antigen and are present at critical left-right and rostrocaudal boundaries during a period of cell proliferation, movement, and migration that produces the nervous system. Thus the Lan3-2 surface glycoprotein or the cells expressing it are candidates for involvement in axon fasciculation, cell migration, and directed axonal growth.

Animals↗

Differential expression of neuron-glia cell adhesion molecule (Ng-CAM) on developing axons and growth cones of interneurons in the chick embryo spinal cord: an immunoelectron microscopic study.

To elucidate the role of neuron-glia cell adhesion molecule (Ng-CAM) in axonal pathway formation of avian spinal interneurons, we have examined the ultrastructural expression of Ng-CAM in the developing spinal cord, by using a preembedding immunocytochemical method. Ng-CAM immunoreactivity was punctate and was restricted to cell surfaces. In accordance with our previous light microscopic observations (Shiga et al., '90), the earliest developing spinal interneurons were Ng-CAM-positive on their cell bodies, axons, and growth cones. Axons and growth cones that were either fasciculated or in contact with each other strongly expressed Ng-CAM, thus indicating the possible involvement of Ng-CAM in fasciculation of axons and in the contact guidance of growth cones along preexisting axons. By using higher resolution immunoelectron microscopy, the present study has also revealed new information on the subcellular localization of Ng-CAM on developing spinal interneurons, neuroepithelial cells, and floor plate cells. Although Ng-CAM immunoreactivity was prominent on both axons and growth cones, these structures were Ng-CAM-negative when they contacted the basal lamina around the spinal cord. By contrast, Ng-CAM was detectable on the surface of both neuroepithelial cells and floor plate cells only when they made contact with the Ng-CAM-positive axons and growth cones of interneurons. These results suggest that the subcellular distribution of Ng-CAM is regulated differentially, depending on the apposing cell surfaces, and that such differential and developmentally regulated expression may contribute to the elongation, fasciculation, and guidance of spinal axons.

Animals↗