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PubMed1998

A functional interaction between the neuronal adhesion molecules TAG-1 and F3 modulates neurite outgrowth and fasciculation of cerebellar granule cells.

F3 and TAG-1 are two closely related adhesion glycoproteins of the Ig superfamily that are both expressed by the axons of cerebellar granule cells. In an in vitro system in which cerebellar granule cells were cultured on monolayers of transfected Chinese hamster ovary (CHO) cells, we show that F3 and TAG-1 interact functionally. F3 transfectants have been shown to inhibit outgrowth and induce fasciculation of granule cell neurites. By contrast TAG-1 transfectants have no effect on these events. However, when TAG-1 is coexpressed with F3, the inhibitory effect of F3 is blocked. Two possible mechanisms may account for this functional interaction: (1) either TAG-1 and F3 compete for the same neuronal receptor, and in favor of this we observed that binding sites for microspheres conjugated with F3 and TAG-1 are colocalized on the granule cell growth cones, (2) or alternatively, F3 and TAG-1 associate in a multimolecular complex after their binding to independent receptors. Extensive co-clustering of F3 with TAG-1 can in fact be achieved by anti-TAG-1 antibody-mediated cross-linking in double-transfected CHO cells. Moreover, F3 coimmunoprecipitates with TAG-1 in Triton X-100-insoluble microdomains purified from newborn brain. These data strongly suggest that F3 and TAG-1 may associate under physiological conditions to modulate neurite outgrowth and fasciculation of the cerebellar granule cells.

Animals↗
PubMed1996

F3 neuronal adhesion molecule controls outgrowth and fasciculation of cerebellar granule cell neurites: a cell-type-specific effect mediated by the Ig-like domains.

F3 is a glycane phosphatidylinositol-anchored neuronal adhesion glycoprotein which consists of immunoglobulin (Ig) domains and fibronectin type III repeats. Here we showed that total F3 or F3-Ig domains when presented as membrane components of CHO transfected cells influenced growth cone morphology, strongly inhibited outgrowth, and induced fasciculation of cerebellar granule cell axons. An F3-Ig-Fc chimera induced neurite fasciculation from cerebellar neuron aggregates when used as a coated substrate but not in the soluble form. The F3 effect on neurite elongation is highly specific for neuronal cell types since under the same experimental conditions it did not modify neurite outgrowth of hippocampal neurons and was shown to stimulate elongation of neurites from sensory neurons in both membrane-anchored and soluble form. Our results provide evidence to extend the proposed role of F3 and strongly suggest that axonal-growth-controlling molecules may quite generally exert dual actions which are likely to depend on the receptor repertoire of the responding neuron.

Animals↗
PubMed1981

Effect of fazadinium (Fazadon) on muscle fasciculations induced by succinylcholine.

The effects on muscle fasciculations and ease of tracheal intubation of pretreatment with fazadinium before administration of succinylcholine were evaluated in 85 patients. Four dose levels of fazadinium evaluated were 0.05 mg . kg-1, 0.075 mg . kg-1, 0.10 mg . kg-1 and 0.15 mg . kg-1. The 0.05 mg . kg-1 dose did not always prevent succinylcholine-induced muscle fasciculations. The 0.15 mg . kg-1 dose gave poor conditions for tracheal intubation and was therefore discontinued. The 0.075 mg . kg-1 dose seemed optimal. Most patients felt transient pain at the site of the injection during administration of fazadinium, and many had a sensation of drowsiness.

Adult↗
PubMed2004

Identification of a tissue-non-specific homologue of axonal fasciculation and elongation protein zeta-1.

Fasciculation and elongation protein zeta-1 (FEZ1) is a mammalian orthologue of the Caenorhabditis elegans UNC-76 protein involved in the axonal outgrowth and fasciculation and promotes neurite extension of PC12 cells through interaction with protein kinase C zeta (PKCzeta). The gene coding for FEZ2, a homologue of FEZ1, has also been reported in rat and human. In this study, we compared mRNA expression of FEZ1 and FEZ2 in adult rat tissues and mouse embryos by Northern blot and in situ hybridization analyses. In contrast to FEZ1 whose mRNA is expressed almost exclusively in rat brain and temporarily around the neurogenesis stage of mouse embryos, the message for FEZ2 is detected weakly in most tissues and abundantly throughout the mouse embryonic stages. Similar to FEZ1, FEZ2 interacted with PKCzeta and induced neurite extension of PC12 cells when coexpressed with a constitutively active mutant of PKCzeta. These results suggest that FEZ2 plays an important role in the morphological changes of various cells by associating with PKCzeta in a tissue-non-specific manner.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Axon fasciculation defects and retinal dysplasias in mice lacking the immunoglobulin superfamily adhesion molecule BEN/ALCAM/SC1.

The immunoglobulin superfamily adhesion molecule BEN (other names include ALCAM, SC1, DM-GRASP, neurolin, and CD166) has been implicated in the control of numerous developmental and pathological processes, including the guidance of retinal and motor axons to their targets. To test hypotheses about BEN function, we disrupted its gene via homologous recombination and analyzed the resulting mutant mice. Mice lacking BEN are viable and fertile, and display no external morphological defects. Despite grossly normal trajectories, both motor and retinal ganglion cell axons fasciculated poorly and were occasionally misdirected. In addition, BEN mutant retinae exhibited evaginated or invaginated regions with photoreceptor ectopias that resembled the "retinal folds" observed in some human retinopathies. Together, these results demonstrate that BEN promotes fasciculation of multiple axonal populations and uncover an unexpected function for BEN in retinal histogenesis.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed2004

Expression of fasciculation and elongation protein zeta-1 (FEZ1) in the developing rat brain.

Fasciculation and elongation protein zeta-1 (FEZ1) is a mammalian homologue of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth and fasciculation. Recently, we reported that FEZ1 interacts with Disrupted-In-Schizophrenia 1 (DISC1), a product of the candidate gene for schizophrenia, and that the interaction between these proteins has a role in neurite outgrowth. This time, we investigated the expression of FEZ1 and DISC1 in the developing rat brain using in situ hybridization. Both FEZ1 and DISC1 showed high levels of expression, especially in developing hippocampal neurons. These findings suggest the potential involvement of FEZ1 and DISC1 in the formation of hippocampal neural circuits.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Neurite elongation on chondroitin sulfate proteoglycans is characterized by axonal fasciculation.

In the developing or regenerating nervous system, migrating growth cones are exposed to regulatory molecules that positively and/or negatively affect guidance. Chondroitin sulfate proteoglycans (CSPGs) are complex macromolecules that are typically negative regulators of growth cone migration in vivo and in vitro. However, in certain cases, neurites sometimes traverse regions expressing relatively high levels of CSPGs, seemingly a paradox. In our continuing efforts to characterize CSPG inhibition in vitro, we manipulated the ratio of CSPGs to growth-promoting laminin-1 to produce a substratum that supports outgrowth of a subpopulation of dorsal root ganglia (DRG) neurites, while still being inhibitory to other populations of DRG neurons [Exp. Neurol. 109 (1990), 111; J. Neurobiol. 51 (2002), 285]. This model comprises a useful tool in the analysis of mechanisms of growth cone guidance and is particularly useful to analyze how CSPGs can be inhibitory under some conditions, and growth permissive under others. We grew embryonic (E9-10) chicken DRG neurons on nervous system-isolated, substratum-bound CSPGs at a concentration that supports an intermittent pattern of outgrowth, alternating with regions adsorbed with growth-promoting laminin-1 alone, and analyzed outgrowth behaviors qualitatively and quantitatively. A novel finding of the study was that DRG neurites that elongated onto CSPGs were predominantly fasciculated, but immediately returned to a defasciculated state upon contact with laminin-1. Further, cursory inspection suggests that outgrowth onto CSPGs may be initially accomplished by pioneer axons, along which subsequent axons migrate. The outgrowth patterns characterized in vitro may accurately reflect outgrowth in vivo in locations where inhibitory CSPGs and growth-promoting molecules are coexpressed, e.g., in the developing retina where fasciculated outgrowth may be instrumental in the guidance of retinal ganglion cells from the periphery to the optic fissure.

Animals↗
PubMed1996

Fasciculated intramedullary pinning of metacarpal fractures.

We reviewed 20 patients with 23 displaced extraarticular fractures of the distal end of the long metacarpals, treated by fasciculated pinning. At a mean follow-up of 5 years, all the patients were subjectively satisfied with the result. All the patients but one, who fractured four metacarpals, had a normal range of motion. The average grip strength was 43.4 kg for the operated side compared to 43.4 kg for the uninjured hand. Radiologically, the fractured fifth metacarpal had a shortening of 2.2 mm compared to a control group, whereas the volar angulation was 16.6 degrees (13.2 degrees for the control group). The technique of intramedullary fasciculated pinning is a reliable alternative when conservative treatment of fractures of the metacarpal neck has failed or is inappropriate. The procedure provides sufficient stability to allow early mobilization and a good functional result.

Adolescent↗
PubMed2002

The C. elegans hmr-1 gene can encode a neuronal classic cadherin involved in the regulation of axon fasciculation.

Nervous system morphogenesis is characterized by extensive interactions between individual axon growth cones and their cellular environments. Selective cell adhesion is one mechanism by which the growth of an axon can be modulated, and members of the classic cadherin group of cell adhesion molecules have been shown to play a role in this process in both vertebrates and Drosophila. In Drosophila, there are two classic cadherins: one involved primarily in regulating the morphogenesis of epithelia, and the other, DN-cadherin, required almost exclusively in neuronal development. In contrast, C. elegans has a single classic cadherin gene, hmr-1, whose function is required for epithelial morphogenesis. We show here that hmr-1 also encodes a second classic cadherin via a novel mechanism involving an alternative, neuron-specific promoter, coupled with alternative splicing. This novel HMR-1 isoform is very similar to DN-cadherin, and a mutant strain that specifically lacks the function of this isoform displays defects in the fasciculation and outgrowth of a subset of motor neuron processes; a phenotype that resembles loss of DN-cadherin function in Drosophila. These results indicate that Drosophila and C. elegans share a conserved, cadherin-dependent mechanism involved in regulating axonal patterning and fasciculation.

Alternative Splicing↗
PubMed1990

Distribution of uncrossed and crossed retinofugal axons in the cat optic nerve and their relationship to patterns of fasciculation.

The course of optic axons that take different routes at the chiasm have been traced through horizontally sectioned optic nerves in the cat, after unilateral injections of horseradish peroxide into the optic tract. Behind the eye and for most of the course of the nerve, nearly all of the axons that remain uncrossed at the chiasm are located in a retinotopically appropriate position, in the lateral aspect of the nerve. However, in the most caudal segment of the nerve an increasing proportion of these axons are located in regions that are retinotopically inappropriate. Just before the nerve joins the chiasm, uncrossed axons can be found across the full medio-lateral extent of the nerve, although there is still a relative increase in their density laterally. Labeled axons that cross at the chiasm course in a relatively parallel manner along the greater proportion of the nerve. However, in the caudal segment of the nerve their relative positions change and they appear to course in an irregular manner. This occurs where the uncrossed projection becomes increasingly more widespread. Axons in the optic nerve are grouped into fascicules. This pattern of organization also changes in the caudal region of the nerve. Although clear fascicular patterns are present along the greater part of the nerve, they become progressively less distinct caudally. The change in the pattern of fasciculation occurs over the same region of the nerve as the relative changes in axon trajectory and distribution. These results demonstrate that irrespective of chiasmatic route, optic axons in the cat are reorganized in the caudal segment of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

ON direction-selective ganglion cells in the rabbit retina: dendritic morphology and pattern of fasciculation.

ON direction-selective (DS) ganglion cells were identified by electrophysiological recordings in DAPI labeled, isolated rabbit retinas. Their responses to a flashing spot were sustained. Their responses to moving stimuli were strong in the preferred direction and weak in the null direction. Injection of the recorded cells with Lucifer yellow revealed that the cells had a distinct dendritic morphology, consistent with that described previously (Buhl & Peichl, 1986; Amthor et al., 1989; Famiglietti, 1992a). When neighboring cells were injected, an extensive dendritic co-fasciculation was observed. The pattern of fasciculation restricts the possible synaptic connections of the ON DS cell.

Animals↗
PubMed1995

Calsensin: a novel calcium-binding protein expressed in a subset of peripheral leech neurons fasciculating in a single axon tract.

The mAb lan3-6 recognizes a cytosolic antigen which is selectively expressed in the growth cones and axons of a small subset of peripheral sensory neurons fasciculating in a single tract common to all hirudinid leeches. We have used this antibody to clone a novel EF-hand calcium-binding protein, calsensin, by screening an expression vector library. A full-length clone of 1.1 kb identified by the antibody was isolated and sequenced. In situ hybridizations with calsensin probes and antibody staining using new polyclonal antisera generated against calsensin sequence demonstrate that calsensin indeed corresponds to the lan3-6 antigen. Calsensin consists of 83 residues with a calculated molecular mass of 9.1 kD that contains two helix-loop-helix domains. The calcium-binding domains are likely to be functional in vivo since a fusion protein derived from the calsensin clone binds 45Ca2+ in vitro. Immunoaffinity purification experiments with the lan3-6 antibody shows that a large 200,000 M(r) protein selectively copurifies with calsensin in two different leech species. These results suggest that calsensin may be functioning as a trigger protein which interacts with the larger protein. These data are consistent with the hypothesis that calsensin may mediate calcium-dependent signal transduction events in the growth cones and axons of this small group of sensory neurons which fasciculate in a single axon tract.

Amino Acid Sequence↗
PubMed1986

Enflurane inhibits muscle fasciculations caused by suxamethonium in children.

Eighty-three children with a mean age of 2.7 years were anaesthetized with either thiopental 5 mg/kg followed by suxamethonium 1.5 mg/kg i.v. or with enflurane 5 vol% in 70% nitrous oxide in oxygen via a face mask. In the enflurane group, venepuncture was performed when the children were unconscious, 1.8 +/- 0.05 (s.e.) min after the start of anaesthesia. After enflurane, suxamethonium 1, 1.5 or 2 mg/kg was administered i.v. for endotracheal intubation. The incidence and duration of muscle fasciculations after suxamethonium were significantly lower (P less than 0.01) in the enflurane groups than in the thiopental group. The fasciculation index was significantly lower (P less than 0.01) in the enflurane groups than in the thiopental group. In the enflurane groups, intubating conditions were better (P less than 0.05) in the children treated with suxamethonium 2 mg/kg than in those treated with suxamethonium 1 mg/kg.

Child↗
PubMed2006

Bronchial involvement in the cramp-fasciculation syndrome.

BACKGROUND/AIMS: Cramp-fasciculation syndrome (CFS) is an acquired, chronic, usually benign and rather heterogeneous condition with isolated fasciculations and muscle cramps generally induced by physical exercise. They commonly involve calf and quadriceps muscles. The pathophysiology of CFS is related to peripheral nerve hyperexcitability, most often located at the motor nerve terminal or intramuscular arborization. METHODS: A 21-year-old man presented with a progressive syndrome of bronchospasm, cramps and muscle twitches related to physical exercise. Spirography showed bronchial hyperresponsiveness, so he received inhaled corticosteroids and beta2-agonists that improved respiratory symptoms. Electrodiagnostic studies were consistent with CFS. Gabapentin was then introduced. RESULTS: Both respiratory and muscle symptoms improved. A new spirogram after all inhaled medication had been discontinued was normal. CONCLUSION: This picture suggests a concomitant involvement of the peripheral motor nerves of both skeletal and airway autonomic smooth muscle, a presentation not previously reported in CFS.

Administration, Inhalation↗
PubMed1992

[Fractures of the humeral shaft: role of fasciculated nailing using Hackethal's method. Apropos of 129 cases].

This retrospective study was based on 141 diaphyseal fractures of the humerus, treated by Hackethal fasciculated pinning, among 371 fractures followed up during 10 years in our department. There were six preoperative radial paralyses. The mean consolidation delay was 65 days. Six fractures did not unite and there was no sepsis. The only immediate neurological postoperative complication was a regressive cubital paralysis. 72 fractures could be followed-up with a mean of 4 years, to establish a functional result chart. 94.4 per cent of the results were good and very good, 2 shoulder stiffness and only one elbow stiffness. The displaced fractures of the humeral diaphysis on D2 to D5 zones, as well as pathological fractures are good indications for Hackethal fasciculated pinning.

Bone Nails↗
PubMed1998

Differential fasciculation of follicular nerves for transferring specifically localized cues of the vibrissa rudiments to the central trigeminal sensory system in mice, as exploited with DiI and DiA labeling.

Vibrissa connections play a decisive role in setting the somatotopic coordinates in the trigeminal sensory system. Although previous studies have examined the development of peripheral patterning, certain questions are still in dispute, for example, the way vibrissa connections are structured, and the relationship between periphery and central organization, and ganglion cell organization. In order to fill the blanks left by previous studies, the extension of ganglionic branches and the formation of vibrissa connections were reexamined by using fluorescent carbocyanin dyes, DiI and DiA, during embryonic days 10 to 14 in mouse. Whole-mount preparations satisfactorily demonstrated the ganglionic fiber system, which allowed detailed analysis at both macroscopic and microscopic levels. We show here that the differential fasciculation of follicular nerves is the critical process for organizing vibrissa connections which modulate the initially extending fiber pattern. Follicular nerves developed by fine fibers arising from initially ordered root fascicles, so as to connect with vibrissa rudiments that developed on the facial prominences. During differential fasciculation, ganglion cells were segregated into distinct groups by the vibrissa connections, whereas central fiber terminals did not yet develop specific structures in the nuclear region. In the primary order of the trigeminal sensory system, vibrissa connections in the periphery were organized before those of the central structure. These results indicate that trigeminal ganglion cells have a critical binomial function in order to transfer the somatotopic relations among vibrissa rudiments into the topographic coordinates of the central system.

Animals↗
PubMed1982

A benign motor neuron disorder: delayed cramps and fasciculation after poliomyelitis or myelitis.

Two patients had a delayed syndrome of benign fasciculation after complete recovery from paralytic poliomyelitis and a third had the syndrome after an attack of purely motor myelitis. Myalgia was prominent in all three, and two had frequent cramps. Denervation hypertrophy occurred in two. The patients were observed for at least three years, and no new weakness was seen. These cases suggest that some chronic diseases of motor neurons may be benign.

Adult↗