Nitric oxide (NO) is an atypical neurotransmitter synthesized by the enzyme nitric oxide synthase (NOS) during many stages of the Xenopus laevis life cycle. This research investigates whether the gas NO is involved in axon guidance, the neurodevelopmental process in which axons travel through the brain to their appropriate target locations to form ...

BackgroundDuring development axons encounter a variety of choice points where they have to make appropriate pathfinding decisions. The optic chiasm is a major decision point for retinal ganglion cell (RGC) axons en route to their target in order to ensure the correct wiring of the visual system. MicroRNAs (miRNAs) belong to the class ...

Dopaminergic neurons from the ventral mesencephalon/diencephalon (mesodiencephalon) form vital pathways constituting the majority of the brain's dopamine systems. Mesodiencephalic dopaminergic (mdDA) neurons extend longitudinal projections anteriorly through the diencephalon, ascending toward forebrain targets. The mechanisms by which mdDA axons initially navigate through the ...

SummaryNavigating axons respond to environmental guidance signals, but can also follow axons that have gone before�pioneer axons. Pioneers have been studied extensively in simple systems, but the role of axon-axon interactions remains largely unexplored in large vertebrate axon tracts, where ...

During early vertebrate forebrain development, pioneer axons establish a symmetrical scaffold descending longitudinally through the rostral forebrain, thus forming the tract of the postoptic commissure (TPOC). In mouse embryos, this tract begins to appear at embryonic day 9.5 (E9.5) as a bundle of axons tightly constrained at a specific dorsoventral level. ...

Motor neurons are functionally related, but represent a diverse collection of cells that show strict preferences for specific axon pathways during embryonic development. In this article, we describe the ligands and receptors that guide motor axons as they extend toward their peripheral muscle targets. Motor neurons share similar guidance molecules with ...

BackgroundThe dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate ...

Recurrent seizures can induce mossy fiber sprouting (MFS), of the hippocampal dentate gyrus, and synaptic reorganization in mature brain. This changes local circuits and provides a structural basis for epileptogenesis in the hippocampus. However, the mechanisms of MFS and synaptic reorganization still remain unclear. Neural-cadherin (N-cadherin), a calcium adhesion molecule, plays an important ...

the midline in the ventral acoustic stria (VAS) are primarily located in the ventral cochlear nucleus (VCN the embryonic VCN for these studies. VCN axons extend toward the midline as early as E13, with many axons crossing by E14.5. During this time, netrin-1 and slit-1 RNAs are expressed at the brainstem midline

The initial step of retinal ganglion cell (RGC) axon pathfinding involves directed growth of RGC axons toward the center of the retina, the optic disc, a process termed �intraretinal guidance�. Due to the accessibility of the system, and with various embryological, molecular, and genetic approaches, significant progress has been ...

Multiple molecular cues guide neuronal axons to their targets during development. Previous studies in vitro have shown that mechanical stimulation also can affect axon growth; however, whether mechanical force contributes to axon guidance in vivo is unknown. We investigated the role of muscle contractions in the guidance of zebrafish ...

Multiple molecular cues guide neuronal axons to their targets during development. Previous studies in vitro have shown that mechanical stimulation also can affect axon growth, however whether mechanical force contributes to axon guidance in vivo is unknown. We have investigated the role of muscle contractions in the guidance of ...

The developing optic pathway has proven one of the most informative model systems for studying mechanisms of axon guidance. The first step in this process is the directed extension of retinal ganglion cell (RGC) axons within the optic fibre layer (OFL) of the retina towards their exit point from the eye, the optic disc. Previously, we have shown that the ...

AbstractThe developing optic pathway has proven one of the most informative model systems for studying mechanisms of axon guidance. The first step in this process is the directed extension of retinal ganglion cell (RGC) axons within the optic fibre layer (OFL) of the retina towards their exit point from the eye, the optic disc. Previously, we have shown ...

Developing neurons use a combination of guidance cues to assemble a functional neural network. A variety of proteins immobilized within the extracellular matrix (ECM) provide specific binding sites for integrin receptors on neurons. Integrin receptors on growth cones associate with a number of cytosolic adaptor and signaling proteins that regulate cytoskeletal dynamics and cell adhesion. Recent ...

Formation of the neural network requires concerted action of multiple axon guidance systems. How neurons orchestrate expression of multiple guidance genes is poorly understood. Here, we show that Drosophila T-box protein Midline controls expression of genes encoding components of two major guidance systems: Frazzled, ROBO, and Slit. In midline mutant, expression of all these ...

Determining how axon guidance receptors transmit signals to allow precise pathfinding decisions is fundamental to our understanding of nervous system development and may suggest new strategies to promote axon regeneration after injury or disease. Signaling mechanisms that act downstream of four prominent families of ...

The study of spinal nerve trajectories in higher vertebrate embryos has revealed an inherent polarity within somites along the antero-posterior axis, and provides a simple system in which to study the factors that influence axon pathfinding. We argue that the orientation of spinal axons is determined by the simultaneous operation of ...

During development of the vertebrate visual system, retinal ganglion cell (RGC) axons follow a precise path toward their midbrain targets. Although much is known about the cues that direct RGC axons once they have left the optic disc, less is known about the guidance of axons at earlier stages, when RGCs first send out their ...

In the retinotectal projection, the Eph receptor tyrosine kinase ligands ephrinA2 and ephrinA5 are differentially expressed not only in the tectum, but also in a high-nasal-to-low-temporal pattern in the retina. Recently, we have shown that retrovirally driven overexpression of ephrinA2 on retinal axons leads to topographic targeting errors of temporal ...

Many genes that affect axon pathfinding and cell migration have been identified. Mechanisms by which these genes and the molecules they encode interact with one another in pathways and networks to control developmental events are unclear. Rac GTPases, the cytoskeletal signaling molecule Enabled, and NIK kinase have all been implicated in regulating ...

This article reviews symptoms and signs of aberrant axon connectivity in humans, and summarizes major human genetic disorders that result, or have been proposed to result, from defective axon guidance. These include corpus callosum agenesis, L1 syndrome, Joubert syndrome and related disorders, horizontal gaze palsy with progressive ...

Netrin has been implicated in retinal ganglion cell (RGC) axon pathfinding in a number of species. In Xenopus laevis, RGC axons reaching their target in the optic tectum can be repelled by a netrin-1 gradient in vitro, suggesting that netrin may also function in wiring events that follow successful axon ...

Purpose: Heparan sulfate (HS) is abundantly expressed in the developing neural retina; however, their role in the intraretinal axon guidance of retinal ganglion cells (RGCs) remains unclear. In this study, we examined whether HS was essential for the axon guidance of RGCs towards the optic nerve head. Methods: We conditionally ablated the gene encoding the ...

The neural and vascular systems share common guidance cues that have direct and independent signaling effects on nerves and endothelial cells. Here, we show that zebrafish Netrin 1a directs Dcc-mediated axon guidance of motoneurons and that this neural guidance function is essential for lymphangiogenesis. Specifically, Netrin 1a secreted by the muscle pioneers at the ...

Laminin is known to provide a highly permissive substratum and in some cases directional information for axon outgrowth in vitro. However, there is still little known about laminin function in guiding axons in vivo. We investigated the axon guidance role of laminin-alpha1 in the developing zebrafish nervous system. Analysis of ...

Early events in the axonal tract formation from mammillary bodies remain poorly understood. In the present study, we reported an aberrant pattern of axonal projections from mammillary bodies to the dorsal thalamus in mice lacking the transcription factor Pax6. We found that Netrin-1 was ectopically up-regulated and that both Slit1 and ...

The segmental arrangement of spinal nerves in higher vertebrate embryos provides a simple system in which to study the factors that influence axon pathfinding. Developing motor and sensory axons are intimately associated with surrounding tissues that direct axon guidance. We argue that two distinct guidance ...

During formation of the optic projection in astray/robo2 mutant zebrafish, optic axons exhibit rostro-caudal pathfinding errors, ectopic midline crossing and increased terminal arbor size. Here we show that these errors persist into adulthood, even when robo2 function is conditionally reduced only during initial formation of the optic projection. Adult ...

Within an axon bundle, one or two are pioneering axons and the rest are follower axons. Pioneering axons are projected first and the follower axons are projected later but follow a pioneering axon(s) pathway. It is not clear whether the pioneering axons ...

Endocannabinoids, particularly 2-arachidonoyl glycerol (2-AG), impact the directional turning and motility of a developing axon by activating CB₁ cannabinoid receptors (CB₁Rs) in its growth cone. Recent findings posit that sn-1-diacylglycerol lipases (DAGL?/?) synthesize 2-AG in the motile axon segment of ...

Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by ...

Statoacoustic ganglion (SAG) neurons send their peripheral processes to navigate into the inner ear sensory organs where they will ultimately become post-synaptic to mature hair cells. During early ear development, neuroblasts delaminate from a restricted region of the ventral otocyst and migrate to form the SAG. The pathfinding mechanisms employed by the processes of SAG ...

Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development ...

Zebrafish embryos offer a unique opportunity to investigate the mechanisms by which nicotine exposure impacts early vertebrate development. Embryos exposed to nicotine become functionally paralyzed by 42 hpf suggesting that the neuromuscular system is compromised in exposed embryos. We previously demonstrated that secondary spinal motoneurons in nicotine-exposed embryos were delayed in development ...

Migrating cells and growth cones extend lamellipodial and filopodial protrusions that are required for outgrowth and guidance. The mechanisms of cytoskeletal regulation that underlie cell and growth cone migration are of much interest to developmental biologists. Previous studies have shown that the Arp2/3 complex and UNC-115/abLIM act redundantly to mediate growth cone lamellipodia and filopodia ...

Migrating cells and growth cones extend lamellipodial and filopodial protrusions that are required for outgrowth and guidance. The mechanisms of cytoskeletal regulation that underlie cell and growth cone migration are of much interest to developmental biologists. Previous studies have shown that the Arp2/3 complex and UNC-115/abLIM act redundantly to mediate growth cone lamellipodia and filopodia ...

During development of the primary olfactory system, sensory axons project from the nasal cavity to the glomerular layer of the olfactory bulb. In the process axons can branch inappropriately into several glomeruli and sometimes over-shoot the glomerular layer, entering the deeper external plexiform layer. However in the adult, axons ...

Mutations in an 8 kDa (8x10(3) Mr) cytoplasmic dynein light chain disrupt sensory axon trajectories in the imaginal nervous system of Drosophila. Weak alleles are behaviorally mutant, female-sterile and exhibit bristle thinning and bristle loss. Null alleles are lethal in late pupal stages and alter neuronal anatomy within the imaginal CNS. We utilized P[Gal4] inserts to ...

This report combines microfabricated, multi-compartment chambers and protein-micropatterned surfaces into a new platform for the study of localized, sub-cellular signaling on axon guidance. We focus on the specific question of local crosstalk between N-cadherin and fibroblast growth factor receptor (FGFR) signaling. Motor neurons differentiated from embryonic stem cells extend ...

Axon guidance cues contributing to the development of eye-specific visual projections to the lateral geniculate nucleus (LGN) have not previously been identified. Here we show that gradients of ephrin-As and their receptors (EphAs) direct retinal ganglion cell (RGC) axons from the two eyes into their stereotyped pattern of layers in the LGN. Overexpression ...

N-cadherin is a classical type I cadherin that contributes to the formation of neural circuits by regulating growth cone migration and the formation of synaptic contacts. This study analyzed the role of N-cadherin in primary motor axons growth during development of the zebrafish (Danio rerio) embryo. After exiting the spinal cord, primary motor axons ...

Netrin-1 influences retinal ganglion cell (RGC) axon pathfinding and also participates in the branching and synaptic differentiation of mature RGC axons at their target. To investigate whether netrin also serves as an early target recognition signal in the brain, we examined the dynamic behavior of Xenopus RGC ...

Most axons in the vertebral central nervous system are myelinated by oligodendrocytes. Myelin protects and insulates neuronal processes, enabling the fast, saltatory conduction unique to myelinated axons. Myelin disruption resulting from trauma and biochemical reaction is a common pathological event in spinal cord injury and chronic neurodegenerative ...

Metathoracic limb buds have been unilaterally ablated from locust embryos at 25 to 30% of embryonic development and the effect of this operation on the axon morphology of the motorneuron fast extensor tibiae (FETi) observed at later embryonic stages. In control embryos this neuron sends a single axon out the main leg nerve, nerve 5, to the extensor tibiae ...

One of the most fascinating processes during nervous system development is the establishment of stereotypic neuronal networks. An essential step in this process is the outgrowth and precise navigation (pathfinding) of axons and dendrites towards their synaptic partner cells. This phenomenon was first described more than a century ago and, over the past ...

SUMMARYNeuronal migration and axon guidance constitute fundamental processes in brain development that are generally studied independently. Although both share common mechanisms of cell biology and biochemistry, little is known about their coordinated integration in the formation of neural circuits. Here we show that the development of the thalamocortical projection, one of ...

Organisms with bilateral symmetry elaborate patterns of neuronal projections connecting both sides of the central nervous system at all levels of the neuraxis. During development, these so-called commissural projections navigate across the midline to innervate their contralateral targets. Commissural axon pathfinding has been extensively studied over the ...

Ena/VASP family proteins are required for accurate axon pathfinding in developing Drosophila, Caenorhabditis elegans, and mouse nervous systems. Recent papers by Bear et al. and Svitkina et al. provide evidence that Ena/VASP proteins regulate actin filament elongation in the lamellipodia and filopodia of nonneuronal cells. Neuronal growth cones use ...

The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these ...

Dithiocarbamates (DTCs), such as disulfiram, have been used in aversion therapy for alcoholism even though an inherent toxicity is induced, which is related mainly to peripheral neuropathy and is associated with behavioural and neurological complications. At anatomical and histopathological levels, DTCs affect structural elements in nervous tissue, such as axonal degeneration ...

As a neuron differentiates, it adopts a suite of features specific to its particular type. Fly photoreceptors are of two types: R1-R6 that innervate the first optic neuropile, the lamina, and R7-R8 that innervate the second, the medulla. Photoreceptors R1-R6 normally have large light-absorbing rhabdomeres, express Rhodopsin1 and have synaptic terminals that innervate the lamina. In Drosophila ...

Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA ...

Aberrant trafficking of the high-affinity choline transporter in AP-3-deficient mice Hidemi Misawa-affinity choline transporter (CHT) is expressed in cholinergic neurons and efficiently transported to axon difference in synaptosomal choline uptake activity is detected, consistent with the existence of a large

Purpose.To use a laser-induced ocular hypertension (LIOH) mouse model to examine the optic nerve head (ONH) expression of EphB/ephrin-B, previously shown to be upregulated in glaucomatous DBA/2J mice. To relate ephrin-B reverse signaling with states of axonal response to disease.Methods.LIOH was induced unilaterally in CD-1 mice by laser photocoagulation of limbal and ...

In the developing nervous system, pathfinding axons navigate through a series of intermediate targets in order to form synaptic connections. Vertebrate spinal commissural axons extend toward and across the floor plate (FP), a key intermediate target located at the ventral midline (VM). Subsequently, post-crossing commissural ...

A key problem in using genetics to dissect the wiring of the mammalian brain lies in discovering which of the billions of neural connections have been disrupted by a particular mutation. A novel gene-trap approach targets the genes involved in brain wiring and labels the axons of neurons expressing those genes, enabling the effects of mutations to be observed directly.

Thalamocortical projections convey visual, somatosensory and auditory information to the cerebral cortex. A recent report in Neural Development shows how a forward genetic screen has enabled the identification of novel mutations affecting specific decision points of thalamocortical axon pathfinding.See research article: ...

Axon outgrowth and pathfinding occurs through a complex series of interacting biochemical signaling pathways that regulate the motility of neuronal growth cones. Over the past 30 years, Paul Letourneau and his students have explored the molecular basis of growth cone motility and have contributed immensely to this field. In celebration of his 65th ...

pathfinding event by showing that two of these phosphatases regulate repulsion from the CNS midline. Axon guidance at the midline has been 801Development 127, 801-812 (2000) Printed in Great Britain � The Company are necessary for repulsion of growth cones from the midline of the embryonic central nervous system. Repulsion

to the devel- opmental problem of axonal guidance, since growth cones appear to articulate pathfinding previously shown that Aplysia bag cell neurons undergo growth cone-target interactions in vitro that involve stereotypic changes in growth cone motility and cytoskeletal structure (Lin and Forscher, 1993). During

Axon path-finding plays an important role in normal and pathogenic brain development as well as in neurological regenerative medicine. In both scenarios, axonal growth is influenced by the microenvironment including the soluble molecules and contact-mediated signaling from guiding cells and cellular matrix. Microfluidic devices are a ...

The chemokine SDF1 activates a cAMP mediated signaling pathway which antagonizes retinal responses to the midline repellent slit. Using male and female zebrafish (Danio rerio), we show that knocking down the calmodulin activated adenylate cyclase ADCY8 makes retinal axons insensitive to the SDF1. Experiments in vivo confirm a mutual antagonism between slit signaling and ADCY8 ...

The neural and vascular systems share common guidance cues that have direct and independent signaling effects on nerves and endothelial cells. Here, we show that zebrafish Netrin 1a directs Dcc-mediated axon guidance of motoneurons and that this neural guidance function is essential for lymphangiogenesis. Specifically, Netrin 1a secreted by the muscle pioneers at the ...

One challenging question in neurogenesis concerns the identification of cues that trigger axonal growth and pathfinding to form stereotypic neuronal networks during the construction of a nervous system. Here, we show that in Drosophila, Engrailed (EN) and Gooseberry-Neuro (GsbN) act together as cofactors to build the posterior commissures (PCs), which ...

Extracellular matrix (ECM) components regulate neurite outgrowth in tissue culture and in vivo. Live imaging of phosphotyrosine (PY) signals revealed that Xenopus laevis growth cones extending on permissive ECM substrata assemble adhesive point contacts containing enriched levels of tyrosine-phosphorylated proteins. Whereas focal adhesion kinase (FAK) signaling is dispensable for the assembly of ...

At early embryonic stages, zebrafish spinal neuron subtypes can be distinguished and accessed for physiological studies. This provides the opportunity to determine electrophysiological properties of different spinal motor neuron subtypes. Such differences have the potential to then regulate, in a subtype-specific manner, activity-dependent developmental events such as axonal ...

Longitudinal axons provide connectivity between remote areas of the nervous system. Although the molecular determinants driving commissural pathway formation have been well characterized, mechanisms specifying the formation of longitudinal axon tracts in the vertebrate nervous system are largely unknown. Here, we study axon guidance ...

BackgroundIn addition to its well-known expression in dorsal telencephalic progenitor cells, where it regulates cell proliferation and identity, the transcription factor Pax6 is expressed in some ventral telencephalic cells, including many postmitotic neurons. Its functions in these cells are unknown.ResultsWe generated a new floxed allele of Pax6 and tested the consequences of a highly specific ...

Retinal projections to visual centers in a marsupial mammal, the tammar wallaby (Macropus eugenii), have been investigated after an eye rotation prior to retinal innervation of the brain. Retinal topography to the superior colliculus and dorsal lateral geniculate nucleus was mapped by using laser lesions of the retina and horseradish peroxidase histochemistry. Despite the change in orientation of ...

ABSTRACT: BACKGROUND: The formation of the mammalian central nervous system requires the establishment of complex neural circuits between a diverse array of neuronal subtypes. Here we report that the proneural transcription factor Neurogenin2 (Ngn2) is crucial for the proper specification of cortical axon projections. RESULTS: The genetic loss of Ngn2 in mice results in fewer ...

BackgroundThe formation of the mammalian central nervous system requires the establishment of complex neural circuits between a diverse array of neuronal subtypes. Here we report that the proneural transcription factor Neurogenin2 (Ngn2) is crucial for the proper specification of cortical axon projections.ResultsThe genetic loss of Ngn2 in mice results in fewer callosal ...

Purpose: The outcome of severe peripheral nerve injuries requiring surgical repair (transection and suture) is usually poor. Recent work suggests that direct suture of nerves increases collagen production and provides unfavourable conditions for a proper axonal regrowth. We tested whether entubulation of the hypoglossal nerve into a Y-tube conduit connecting it with the ...

Axonal projections from the retina to the brain are regulated by molecules including the Slit family of ligands [Thompson, H., Barker, D., Camand, O., Erskine, L., 2006a. Slits contribute to the guidance of retinal ganglion cell axons in the mammalian optic tract. Dev. Biol. 296, 476-484, Thompson, H., Camand, O., Barker, D., Erskine, L., 2006b. Slit ...

A set of techniques is described for determining the response of mammalian spinal axons to transection. The logical selection and the advantages of these techniques are discussed. The dorsal column of guinea pig thoracic spinal cord was transected with a tungsten needle and the position of the lesion was marked by a staple-shaped wire device (Foerster: J. Comp. Neurol. ...

In neurons polarized trafficking of vesicle-bound membrane proteins gives rise to the distinct molecular composition and functional properties of axons and dendrites. Despite their central role in shaping neuronal form and function, surprisingly little is known about the molecular processes that mediate polarized targeting of neuronal proteins. Recently, the plus-end-directed ...

The formation of branchiomeric nerves (cranial nerves V, VII, IX and X) from their sensory, motor and glial components is poorly understood. The current model for cranial nerve formation is based on the Vth nerve, in which sensory afferents are formed first and must enter the hindbrain in order for the motor efferents to exit. Using transgenic zebrafish lines to discriminate between motor neurons, ...

Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ...

The corpus callosum (CC) is the main pathway responsible for interhemispheric communication. CC agenesis is associated with numerous human pathologies, suggesting that a range of developmental defects can result in abnormalities in this structure. Midline glial cells are known to play a role in CC development, but we here show that two transient populations of midline neurons also make major ...

The abdomen of adult Drosophila bears mechanosensory bristles with axons that connect directly to the CNS, each hemisegment contributing a separate nerve bundle. Here, we alter the amount of Engrailed protein and manipulate the Hedgehog signalling pathway in clones of cells to study their effects on nerve pathfinding within the peripheral nervous system. ...

The abdomen of adult Drosophila bears mechanosensory bristles with axons that connect directly to the CNS, each hemisegment contributing a separate nerve bundle. Here, we alter the amount of Engrailed protein and manipulate the Hedgehog signalling pathway in clones of cells to study their effects on nerve pathfinding within the peripheral nervous system. ...

Development of both dendrites and axons is important for the formation of neuronal circuits, because dendrites receive information and the axon is responsible for sending signals. In the past decade, extensive studies have revealed many molecules underlying axonal outgrowth and pathfinding. In contrast, much less ...

Extracellular gradients of secreted guidance factors are known to guide axon pathfinding and neuronal migration. These factors are likely to bind to cell surfaces or extracellular matrix, but whether and how they may act in bound gradients remains mostly unclear. In this study, we have developed a new technique for rapid production of stable microscopic ...

Matrix metalloproteinases (MMPs) are widely hypothesized to regulate signaling events through processing of extracellular matrix (ECM) molecules. We previously demonstrated that membrane-associated Mmp2 is expressed in exit glia and contributes to motor axon targeting. To identify possible substrates, we undertook a yeast interaction screen for Mmp2-binding proteins and ...

We studied axonal damage in Alzheimer's disease frontal cortex and hippocampus with a novel monoclonal antibody (SMI 312) against phosphorylated neurofilaments. This antibody immunolabeled, with great detail, the neuropil axonal network. In aged normal cases only a few pyramidal cell perikarya were immunostained. In Alzheimer's disease there was a two- to ...

Monoaminergic neurons (serotonergic (5HT) and dopaminergic (mdDA)) in the brainstem project axons along the anterior-posterior axis. Despite their important physiological functions and implication in disease, the molecular mechanisms that dictate the formation of these projections along the anterior-posterior axis remain unknown. Here we reveal a novel requirement for ...

BackgroundThe trajectory of corticospinal tract (CST) axons from cortex to spinal cord involves a succession of choice points, each of which is controlled by multiple guidance molecules. To assess the involvement of transmembrane semaphorins and their plexin receptors in the guidance of CST axons, we have examined this tract in mutants of Semaphorin-6A ...

The roles of actin-binding proteins in development and morphogenesis are not well understood. The actin-binding protein UNC-115 has been implicated in cytoskeletal signaling downstream of Rac in Caenorhabditis elegans axon pathfinding, but the cellular role of UNC-115 in this process remains undefined. Here we report that UNC-115 overactivity in C. elegans ...

Axon pathfinding and synapse formation rely on precise spatiotemporal localization of guidance receptors. However, little is known about the neuron-specific intracellular trafficking mechanisms that underlie the sorting and activity of these receptors. Here we show that loss of the neuron-specific v-ATPase subunit a1 leads to progressive endosomal guidance ...

Motor growth cones navigate long and complex trajectories to connect with their muscle targets. Experimental studies have shown that this guidance process critically depends on extrinsic cues. In the zebrafish embryo, a subset of mesodermal cells, the adaxial cells, delineates the prospective path of pioneering motor growth cones. Genetic ablation of adaxial cells causes profound ...

Neural cell adhesion molecules (CAMs) are important players during neurogenesis and neurite outgrowth as well as axonal fasciculation and pathfinding. Some of these developmental processes entail the activation of cellular signaling cascades. Pharmacological and genetic evidence indicates that the neurite outgrowth-promoting activity of L1-type CAMs is at ...

The Pax-6 gene encodes a transcription factor that is expressed in regionally restricted patterns in the developing brain and eye. Here we describe Pax-6 expression in the early forebrain (prosencephalon) on embryonic day 9.5 (E9.5) to E10.5 using both whole-mount in situ hybridization and antibody labeling. We find close correlations between Pax-6+ domains and initial neural patterning, and ...

BackgroundCultured spinal motor neurons are a valuable tool to study basic mechanisms of development, axon growth and pathfinding, and, importantly, to analyze the pathomechanisms underlying motor neuron diseases. However, the application of this cell culture model is limited by the lack of efficient gene transfer techniques which are available for other ...

Axons from a distinct group of neurons make contact with dendritic trees of target neurons in clearly segregated and laminated patterns, thereby forming functional units for processing multiple inputs of information in the vertebrate central nervous system. Whether and how dendrites acquire lamina-specific properties corresponding to each pathway is not known. We show here ...

Axons from a distinct group of neurons make contact with dendritic trees of target neurons in clearly segregated and laminated patterns, thereby forming functional units for processing multiple inputs of information in the vertebrate central nervous system. Whether and how dendrites acquire lamina-specific properties corresponding to each pathway is not known. We show here ...

The immune system and nervous system display striking similarities. Fernandis and Ganju discuss yet another example where a protein (Slit) originally identified for its role in modulating axon pathfinding is able to regulate immune cell migration. Slit isoforms expressed in the nervous system interact with members of the Robo receptor family to modify ...

BackgroundDuring development, neuronal growth cones integrate diffusible and contact guidance cues that are conveyed to both actin and microtubule (MT) cytoskeletons and ensure axon outgrowth and pathfinding. Although several post-translational modifications of tubulin have been identified and despite their strong conservation among species, their ...

Iontophoresis of ?(1)-adrenoceptor agonists in the human forearm evoke axon reflex vasodilatation, possibly due to an accumulation of inflammatory agents at the site of iontophoresis. To investigate this possibility, skin sites in the forearm of healthy participants were treated with an anti-inflammatory gel containing ibuprofen 5% before the iontophoresis of the ...

Axonal degeneration is a prominent pathological feature in multiple sclerosis observed over a century ago. The gradual loss of axons is thought to underlie irreversible clinical deficits in this disease. The precise mechanisms of axonopathy are poorly understood, but likely involve excess accumulation of Ca ions. In healthy fibers, ATP-dependent pumps ...

Olfactory axons have been shown to grow aberrantly and form dense collections of axons, termed neuromas, in the olfactory epithelium of rats in which the olfactory bulb was ablated. Likewise, in human olfactory mucosa, collections of neurites have been noted in a variety of disease states, including Alzheimer's disease. We report here ...

Besides initiating and propagating action potentials in established neuronal circuits, voltage-dependent sodium channels sculpt and bolster the functional neuronal network from early in embryonic development through adulthood (e.g., differentiation of oligodendrocyte precursor cells into oligodendrocytes, myelinating axon; competition between neighboring equipotential neurites ...

We previously reported that mice lacking JSAP1 (jsap1-/-) were lethal and the brain of jsap1-/- at E18.5 exhibited multiple types of developmental defects, which included impaired axon projection of the corpus callosum and anterior commissures. In the current study, we examined whether the early telencephalic commissures were formed abnormally from the beginning of initial ...

We previously reported that mice lacking JSAP1 (jsap1^-/-) were lethal and the brain of jsap1^-/- at E18.5 exhibited multiple types of developmental defects, which included impaired axon projection of the corpus callosum and anterior commissures. In the current study, we examined whether the early telencephalic commissures were ...

Netrins are well known for their function as long-range chemotropic guidance cues, in particular in the ventral midline of vertebrates and invertebrates. Over the past years, publications are accumulating that support an additional short-range function for Netrins in diverse developmental processes such as axonal pathfinding and cell adhesion. We describe ...

BackgroundReciprocal interactions between glial cells and olfactory receptor neurons (ORNs) cause ORN axons entering the brain to sort, to fasciculate into bundles destined for specific glomeruli, and to form stable protoglomeruli in the developing olfactory system of an experimentally advantageous animal species, the moth Manduca sexta. Epidermal growth factor receptors ...

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that ...

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that ...

In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of Schwann cell development are known, the signaling pathways that control myelination are incompletely understood. In this study, we show that Gpr126 is essential for myelination and other aspects of peripheral ...

Endocytosis of Eph-ephrin complexes may be an important mechanism for converting cell-cell adhesion to a repulsive interaction. Here, we show that an endocytosis-defective EphA8 mutant forms a complex with EphAs and blocks their endocytosis in cultured cells. Further, we used bacterial artificial chromosome transgenic (Tg) mice to recapitulate the anterior>posterior gradient of EphA in the ...

Eukaryotic organisms utilize microtubule-dependent motors of the kinesin and dynein superfamilies to generate intracellular movement. To identify new genes involved in the regulation of axonal transport in Drosophila melanogaster, we undertook a screen based upon the sluggish larval phenotype of known motor mutants. One of the mutants identified in this screen, roadblock ...

The pathfinder will undergo folding and deployment trials through 2007 to verify its design concept and deployment techniques. The pathfinder is one in a ...

Power for time keeping mechanism of Pathfinder ... Time required to build another Pathfinder ... Choice of pyrotechnic devices � Pathfinder computer ...

Mars Pathfinder Mission. Science and Instruments ... Mars Pathfinder Participating Scientists and Facility Instrument Science Team ...