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At least 793 records · Page 44Linked to original sources
PubMed1995

Peripheral axonal pathway and cleaning behavior are correlated in Drosophila microchaetes.

The notum of Drosophila is covered with evenly spaced small mechanosensory bristles (microchaetes). Four groups of microchaetes can be distinguished on the basis of the pathways followed by the axons of their neurons. In three of the four groups, the axons extend along fibrous processes, the prospective tendons of the adult indirect flight muscles, formed by the epithelial cells. We show that the subdivision into four fasciculation groups is correlated to differences in the cleaning behavior elicited by stimulating the microchaetes.

Animals↗
PubMed1995

Native and recombinant DM-GRASP selectively support neurite extension from neurons that express GRASP.

DM-GRASP (GRASP) is an integral membrane glycoprotein expressed on a restricted set of axons in the developing chick nervous system. We demonstrate that purified GRASP supports neurite extension from the subpopulation of neurons that express GRASP. Sensory, sympathetic, and ciliary neurons express GRASP and extend neurites on a GRASP substrate. In contrast, tectal, diencephalic, and retinal cells express GRASP at a very low level, if at all, and do not extend neurites on a GRASP substrate. Moreover, as GRASP is downregulated on sensory neurons during development, they lose the capacity to extend neurites on a GRASP substrate. Recombinant GRASP produced in a baculovirus expression system is biochemically and functionally identical to GRASP purified from embryonic chick brain. The finding that GRASP selectively supports neurite extension supports the hypothesis that it mediates selective fasciculation via a homophilic binding mechanism.

Activated-Leukocyte Cell Adhesion Molecule↗
PubMed1995

Peripheral neurons depend on CNS-derived guidance cues for proper navigation during leech development.

In leech, major nerve pathways are pioneered by CNS neurons and evidence from dye-injection and antibody experiments suggest that they serve as guides for later differentiating neurons. In this study we have directly tested this hypothesis by examining the consequences of CNS ablation on the navigation in the periphery of a well-defined population of afferent sensory neurons. We show that in the absence of CNS-derived axons the axonal growth cones of this population of peripheral neurons extend with little directionality and instead of forming orderly projections, default into forming circular fasciculated pathways with each other. This suggests that CNS-derived guidance cues are absolutely required for the correct navigation of these peripheral sensory neurons.

Animals↗
PubMed1999

Thalamocortical axons are influenced by chemorepellent and chemoattractant activities localized to decision points along their path.

Thalamocortical axons (TCAs), which originate in dorsal thalamus, project ventrally in diencephalon and then dorsolaterally in ventral telencephalon to their target, the neocortex. To elucidate potentially key decision points in TCA pathfinding and hence the possible localization of guidance cues, we used DiI-tracing to describe the initial trajectory of TCAs in mice. DiI-labeled TCAs extend ventrally on the lateral surface of ventral thalamus. Rather than continuing this trajectory onto the lateral surface of the hypothalamus, TCAs make a sharp lateral turn into ventral telencephalon. This behavior suggests that the hypothalamus is repulsive and the ventral telencephalon attractive for TCAs. In support of this hypothesis, we find that axon outgrowth from explants of dorsal thalamus is biased away from hypothalamus and toward ventral telencephalon when cocultured at a distance in collagen gels. The in vivo DiI analysis also reveals a broad cluster of retrogradely labeled neurons in the medial part of ventral telencephalon positioned within or adjacent to the thalamocortical pathway prior to or at the time TCAs are extending through it. The axons of these neurons extend into or through dorsal thalamus and appear to be coincident with the oppositely extending TCAs. These findings suggest that multiple cues guide TCAs along their pathway from dorsal thalamus to neocortex: TCAs may fasciculate on the axons of ventral telencephalic neurons as they extend through ventral thalamus and the medial part of ventral telencephalon, and chemorepellent and chemoattractant activities expressed by hypothalamus and ventral telencephalon, respectively, may cooperate to promote the turning of TCAs away from hypothalamus and into ventral telencephalon.

Animals↗
PubMed2000

Different isoforms of fasciclin II play distinct roles in the guidance of neuronal migration during insect embryogenesis.

During the formation of the enteric nervous system (ENS) of the moth Manduca sexta, identified populations of neurons and glial cells participate in precisely timed waves of migration. The cell adhesion receptor fasciclin II is expressed in the developing ENS and is required for normal migration. Previously, we identified two isoforms of Manduca fasciclin II (MFas II), a glycosyl phosphatidylinositol-linked isoform (GPI-MFas II) and a transmembrane isoform (TM-MFas II). Using RNA and antibody probes, we found that these two isoforms were expressed in cell type-specific patterns: GPI-MFas II was expressed by glial cells and newly generated neurons, while TM-MFas II was confined to differentiating neurons. The expression of each isoform also corresponded to the motile state of the different cell types: GPI-MFas II was detected on tightly adherent or slowly spreading cells, while TM-MFas II was expressed by actively migrating neurons and was localized to their most motile regions. Manipulations of each isoform in embryo culture showed that they played distinct roles: whereas GPI-MFas II acted strictly as an adhesion molecule, TM-MFas II promoted the motility of the EP cells as well as maintaining fasciculation with their pathways. These results indicate that precisely regulated patterns of isoform expression govern the functions of fasciclin II within the developing nervous system.

Animals↗
PubMed2000

Mechanisms underlying olfactory neuronal connectivity in Drosophila-the atonal lineage organizes the periphery while sensory neurons and glia pattern the olfactory lobe.

Patterning of the antennal lobe of adult Drosophila occurs through a complex interaction between sensory neurons, glia, and central neurons of larval and adult origin. Neurons from the olfactory sense organs are organized into distinct fascicles lined by glial cells. The glia originate from one of the three types of sensory lineages-specified by the proneural gene atonal. Gain-of-function as well as loss-of-function analysis validates a role for cells of the Atonal lineage in the ordered fasciculation of sensory neurons. Upon entry of the antennal nerve to central regions, sensory neurons at first remain closely associated with central glia which lie around the periphery of the lobe anlage. Coincident with the arrival of sensory neurons into the brain, glial precursors undergo mitosis and neural precursors expressing Dachshund appear around the lobe. Sensory neurons and glial cells project into the lobe at around the same time and are likely to coordinate the correct localization of different glomeruli. The influence of sensory neurons on the development of the olfactory lobe could serve to match and lock peripheral and central properties important for the generation of olfactory behavior.

Animals↗
PubMed2001

Cell type-specific expression of fasciclin II isoforms reveals neuronal-glial interactions during peripheral nerve growth.

During the formation of the insect peripheral nervous system (PNS), the cell adhesion receptor fasciclin II has been shown to play a prominent role in axonal fasciculation and synapse formation during motor neuron outgrowth. In the moth Manduca, fasciclin II (MFas II) is expressed both as a transmembrane isoform (TM-MFas II) and a glycosyl phosphatidylinositol-linked isoform (GPI-MFas II). By using RNA and antibody probes, we have shown that these two isoforms are expressed in nonoverlapping patterns: TM-MFas II is expressed exclusively by neurons and becomes localized to their most motile regions, while GPI-MFas II is expressed primarily by the glial cells that ensheath the peripheral nerves. This cell-type specificity of expression allowed us to monitor the nature of neuronal-glial interactions during PNS development. The outgrowth of TM-MFas II-positive axons in many regions preceded the arrival of GPI-MFas II-expressing glial processes that enwrapped them. In a few key locations, however, GPI-MFas II-positive glial cells differentiated before the arrival of the first axons and prefigured their subsequent trajectories. Prior inhibition of GPI-MFas II expression disrupted the subsequent outgrowth of axons at these locations but not elsewhere in the PNS. Our results suggest that the two isoforms of MFas II play distinct roles with respect to cellular motility and nerve formation.

Animals↗
PubMed2002

Effects of L1 blockade on sensory axon outgrowth and pathfinding in the chick hindlimb.

In the developing chick hindlimb, sensory axons, which grow together in bundles as they extend distally, and the motoneuron axons they encounter express the cell adhesion molecule L1. Following injection of function-blocking anti-L1 antibodies into the limb at stage 25, some sensory axons choose inappropriate peripheral nerves even though motoneuron pathfinding is unaffected. Here, to further elucidate L1's role, we assessed the effects of this perturbation using pathway tracing, immune labeling, confocal microscopy, and electron microscopy. After L1 blockade, sensory axons were still bundled and closely apposed. However, clear signs of decreased adhesion were detectable ultrastructurally. Further, sensory axons grew into the limb more slowly than normal, wandering more widely, branching more frequently, and sometimes extending along inappropriate peripheral nerves. Sensory axons that ultimately projected along different cutaneous nerves showed increased intermixing in the spinal nerves, due to errors in pathfinding and also to a decreased ability to segregate into nerve-specific fascicles. These results suggest that, in the highly complex in vivo environment, as in tissue culture, L1 stimulates axon growth and enhances fasciculation, and that these processes contribute to the orderly, timely, and specific growth of sensory axons into the limb.

Animals↗
PubMed2002

EphA4 constitutes a population-specific guidance cue for motor neurons.

Motor neurons in the ventral neural tube project axons specifically to their target muscles in the periphery. Although many of the transcription factors that specify motor neuron cell fates have been characterized, less is understood about the mechanisms that guide motor axons to their correct targets. We show that ectopic expression of EphA4 receptor tyrosine kinase alters the trajectories of a specific population of motor axons in the avian hindlimb. Most motor neurons in the medial portion of the lateral motor column (LMC) extend their axons aberrantly in the dorsal nerve trunk at the level of the crural plexus, in the presence of ectopic EphA4. This misrouting of motor axons is not accompanied by alterations in motor neuron identity, settling patterns in the neural tube, or the fasciculation of spinal nerves. However, ectopic EphA4 axons do make errors in pathway selection during sorting in the plexus at the base of the hindlimb. These results suggest that EphA4 in motor neurons acts as a population-specific guidance cue to control the dorsal trajectory of their axons in the hindlimb.

Animals↗
PubMed2002

Distinct rac activation pathways control Caenorhabditis elegans cell migration and axon outgrowth.

Rac GTPases act as molecular switch in various morphogenic events. However, the regulation of their activities during the development of multicellular organisms is not well understood. Caenorhabditis elegans rac genes ced-10 and mig-2 have been shown to act redundantly to control P cell migration and the axon outgrowth of D type motoneurons. We showed that ced-10 and mig-2 also control amphid axon outgrowth and amphid dendrite fasciculation in a redundant fashion. Our biochemical and genetic data indicate that unc-73, which encodes a protein related to Trio-like guanine nucleotide exchange factor, acts as a direct activator of ced-10 and mig-2 during P cell migration and axon outgrowth of D type motoneurons and amphid sensory neurons. Furthermore, rac regulators ced-2/crkII and ced-5/dock180 function genetically upstream of ced-10 and mig-2 during axon outgrowth of D type motoneurons and act upstream of mig-2 but not ced-10 during P cell migration. However, neither ced-2/crkII nor ced-5/dock180 is involved in amphid axon outgrowth. Therefore, distinct rac regulators control ced-10 and mig-2 differentially in various cellular processes.

Animals↗
PubMed1993

Neurobehavioral changes among workers in some chemical industries in Egypt.

This study investigates the long-term neuropsychiatric manifestations of single or combined chemicals: manganese; zinc phosphide; lead, mercury, and TNT; and pesticides among exposed industrial workers. We found that 75% of the exposed subjects as a whole and 50% of those exposed to each of Zinc phosphide and pesticides presented with more than one neuropsychiatric symptoms or signs. The main signs were mask faces, hyporeflexia, hyperreflexia, peripheral neuropathy, static tremors, radiculopathy, muscle weakness, mental changes, fasciculations and tremors, wasting, hypotonia, abnormal deep reflexes, and sensory hyposthesia. Neurological manifestations were confirmed by electromyography and their severity was related to the duration of exposure and confirmed as well by electroencephalography. These results are discussed and their implications high-lighted.

Adult↗
PubMed1994

Morphology and growth of embryonic, human dorsal root ganglion explants in long-term culture: expression of cell type-specific markers during early differentiation.

Embryonic, human spinal ganglion explants were plated at 5-12 weeks postconceptional age and cultured for 5-50 days on a semisynthetic substrate in a serum-containing culture medium without addition of antibiotics or preconditioned medium. The growth pattern in vitro was found to be age dependent. Five- to 6-week ganglia showed a characteristic semicircular growth pattern with bidirectional extension of neurites on top of a monolayer of supportive cells. Explanted 9- to 10-week ganglia showed an extensive, multidirectional neurite outgrowth with less pronounced proliferation of nonneuronal cells. Neurite extension, fasciculation, cell migration and morphology were studied immunohistochemically with antibodies to neurofilament (NF), S-100, and the Thy-1 glycoprotein. Both NF and S-100 were expressed at 5 weeks gestational age in ganglionic neurons and in proliferating Schwann cells in contact with axonal processes, respectively. NF was homogeneously distributed in both cell somata and neurites, whereas S-100 immunoreactivity showed an intense nuclear and a weaker cytoplasmic distribution in spindle-shaped, bipolar Schwann cells. This staining pattern was conserved during differentiation in long-term culture. Thy-1 was expressed on ganglionic neurites forming fascicles by the third week in culture. However, Thy-1 was never expressed until the total age of 10 weeks. In addition, Thy-1 was found on fibroblasts from the first week in culture. The distribution of Thy-1 on the cytoplasmic membrane was similar in both cell types, showing a coarsely granulated membrane staining. The temporal as well as the spatial expression of differentiation antigens in tissue sections of early embryonic spinal cord and spinal ganglia were very similar to what was observed in vitro.

Antigens, Surface↗
PubMed1994

Extrusion transplantation of Schwann cells into the adult rat thalamus induces directional host axon growth.

In a previous study we found that Schwann cells microtransplanted into the central nervous system rapidly dispersed from the transplantation site and became intimately associated with host grey and white matter. We have now investigated whether this migratory behavior of the donor Schwann cells is compatible with the production of stable, continuous anatomical cell tracks and whether such tracks can induce directional host axon growth. During the gradual withdrawal of a micropipette, highly purified suspensions of cultured adult peripheral nerve Schwann cells were continuously extruded to form a vertical column of cells extending for up to 4 mm through the thalamus and across the choroid fissure into the hippocampus of adult rat hosts. The donor Schwann cells were identified by immunohistochemistry for low-affinity nerve growth factor receptor, vimentin, and Rat 401. Although donor Schwann cells migrated into the host tissues, a large number remained along the axis of the injection track to form a column which was maintained for up to 3 weeks. From 4 days, increasing numbers of parallel, unbranching host RT97-positive axons entered the Schwann cell column in alignment with the long axis of the Schwann cells in the vertical tracks. The axons did not fasciculate directly with each other, but mingled diffusely with the Schwann cells. The Schwann cell tracks were able to convey host axons out of the dorsal thalamus, across the extracellular space of the choroid fissure, and into the ventral hippocampus. Thus, Schwann cells, transplanted in the form of elongated tracks, can establish bridges across boundary membranes in the brain and carry substantial numbers of nerve fibers from one area to another.

Animals↗
PubMed1999

Serum and CNTF stimulate oligodendroglia and reduce fiber outgrowth from striatal cultures.

Organotypic slice cultures of newborn rat striatal tissue displayed an exceptionally dense and fasciculated outgrowth of GABAergic fibers when grown in a chemically defined medium, compared to serum-containing medium. The enhanced fiber growth was not the result of an increased density of GABAergic neurons in the cultures, but coincided with a marked reduction of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase)-immunoreactive cells within and around the cultures. An inverse, causal relationship between the number of CNPase-positive cells, presumably of oligodendroglial lineage, and GABAergic fiber outgrowth was further evidenced by the observation that addition of ciliary neurotrophic factor (CNTF) to the chemically defined medium resulted in both an increase in CNPase-positive cells and a decrease in GABAergic fiber outgrowth. The observations suggest that CNTF and serum indirectly inhibit axonal growth by stimulating oligodendroglial cells.

Animals↗
PubMed1997

4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs.

The extent to which cardiorespiratory infirmity and other sublethal effects of saxitoxin (STX) and tetrodotoxin (TTX) can be reversed by 4-aminopyridine (4-AP) was investigated in guinea pigs chronically instrumented for the concurrent electrophysiological recordings of electrocorticogram (ECoG), diaphragmatic electromyogram (DEMG), Lead II electrocardiogram, and neck skeletal muscle electromyogram. Animals were intoxicated with either STX or TTX (2 and 3 microg/kg, im) to produce a state of progressive cardiorespiratory depression (depicted by decreasing DEMG amplitude, bradypnea, and bradycardia). At the point where cardiorespiratory performance was most seriously compromised (approximately 30 min posttoxin), 4-AP (1 or 2 mg/kg, im) was administered. The therapeutic effect of 4-AP was striking in that, within minutes, the toxin-induced diaphragmatic blockade, bradypnea, bradycardia, and depressed cortical activity were all restored to a level either comparable to, or surpassing, that of control. The optimal 4-AP dose level was determined to be 2 mg/kg (im) based on analyses of cardiorespiratory activity profiles throughout the course of intoxication and 4-AP treatment. At the dose levels (either 1 or 2 mg/kg) used to restore ventilatory function and cardiovascular performance, 4-AP produced no sign of seizures and convulsions. Although less serious secondary effects such as cortical excitant/arousal effect (indicated by ECoG power spectral analysis) and transient periods of skeletal muscle fasciculation were observed, these events were of minor concern particularly in view of the remarkable therapeutic effects of 4-AP.

4-Aminopyridine↗
PubMed1996

Deletions in the extracellular domain of rat trkA lead to an altered differentiative phenotype in neurotrophin responsive cells.

We have investigated the role(s) of conserved sequences in the extracellular domain of rat trkA by generating 5' and 3' deletions and assaying changes in neurotrophin binding, tyrosine kinase activity, and neurite outgrowth. Essential sequences required for both nerve growth factor (NGF) and neurotrophin-3 (NT-3) binding were mapped to the immunoglobulin-like domains. Small deletions in the second immunoglobulin-like domain and in the juxtamembrane region abolished neurotrophin binding. Dose-response curves on cells expressing full-length trkA were identical for NGF and NT-3 (0.1 ng/ml-50 ng/ml) while cells expressing leucine rich motif (LRM) minus receptors required high concentrations of NT-3 (50 ng/ml). Scatchard analysis revealed a loss of high-affinity NT-3, but not NGF, binding to the LRM minus receptor consistent with the neurite dose-response curves. Moreover, cells expressing the LRM minus receptors failed to fasciculate and showed delayed arborization in comparison to cells expressing wild-type trkA, suggesting a possible role for the LRM's in neurotrophin-induced differentiation and in high-affinity NT-3 binding.

Animals↗
PubMed1996

The Eph kinase ligand AL-1 is expressed by rostral muscles and inhibits outgrowth from caudal neurons.

In the peripheral nervous system, neurons derived from specific rostrocaudal levels of the neuraxis selectively synapse on targets that arise from corresponding body positions. To identify molecules involved in such position-dependent connectivity, we used subtractive hybridization to isolate genes selectively expressed in rostral or caudal skeletal muscle. One mRNA that was more abundant in neck than in hindlimb muscles encoded the mouse ortholog of human AL-1 and chick RAGS, membrane-associated ligands of Eph tyrosine kinases that have recently been implicated in cortical axon fasciculation and retinotectal connectivity, respectively. We show here that mouse AL-1 is expressed in discrete regions of the central and peripheral nervous systems and in a subset of developing skeletal muscles. The abundance of AL-1 RNA in immortalized myogenic cell lines derived from rostral muscles is higher than in caudally derived lines, suggesting that levels are heritably maintained. Growth of neurites from cultured sensory ganglia and spinal cords is specifically inhibited by cells expressing AL-1, suggesting that this molecule could serve to guide peripheral axons. The inhibitory effects of AL-1 are position dependent, such that axons derived from caudal (lumbar) ganglia are more affected than those derived from rostral (cervical) ganglia. Together, these results support the notion that Eph kinases and their ligands regulate topographically appropriate neural connectivity in the peripheral nervous system, as well as in the central nervous system.

Amino Acid Sequence↗
PubMed1996

Similarities and differences in the way transmembrane-type ligands interact with the Elk subclass of Eph receptors.

The Eph family of receptor tyrosine kinases and their cell surface bound ligands have been implicated in a number of developmental processes, including axon pathfinding and fasciculation, as well as patterning in the central nervous system. To better understand the complex signaling events taking place, we have undertaken a comparative analysis of ligand-receptor interactions between a subset of ligands, those that are tethered to the cell surface via a transmembrane domain, and a subset of Eph receptors, the so-called Elk subclass. Based on binding characteristics, receptor autophosphorylation, and cellular transformation assays, we find that the transmembrane-type ligands Lerk2 and Elf2 have common and specific receptors within the Elk subclass of receptors. The common receptors Cek10 and Elk bind and signal in response to Lerk2 and Elf2, whereas the Myk1 receptor is specific for Elf2. Elf2, however, fails to signal through Cek5 in a cellular transformation assay, suggesting that Lerk2 may be the preferred Cek5 ligand in vivo. A recently identified third transmembrane-type ligand, Elf3, specifically, but weakly, binds Cek10 and only induces focus formation when activated by C-terminal truncation. This suggests that the physiological Elf3 receptor may have yet to be identified. Knowledge regarding functional ligand-receptor interactions as presented in this study will be important for the design and interpretation of in vivo experiments, e.g., loss-of-function studies in transgenic mice.

3T3 Cells↗