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PubMed2006

A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting.

In the mouse, olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) converge their axons to a specific set of glomeruli in the olfactory bulb. To study how OR-instructed axonal fasciculation is controlled, we searched for genes whose expression profiles are correlated with the expressed ORs. Using the transgenic mouse in which the majority of OSNs express a particular OR, we identified such genes coding for the homophilic adhesive molecules Kirrel2/Kirrel3 and repulsive molecules ephrin-A5/EphA5. In the CNGA2 knockout mouse, where the odor-evoked cation influx is disrupted, Kirrel2 and EphA5 were downregulated, while Kirrel3 and ephrin-A5 were upregulated, indicating that these genes are transcribed in an activity-dependent manner. Mosaic analysis demonstrated that gain of function of these genes generates duplicated glomeruli. We propose that a specific set of adhesive/repulsive molecules, whose expression levels are determined by OR molecules, regulate the axonal fasciculation of OSNs during the process of glomerular map formation.

Animals↗
PubMed2005

Pain and calf hypertrophy associated with spontaneous repetitive discharges treated with botulinum toxin.

OBJECTIVE: To report a case of neurogenic calf hypertrophy associated with root lesion responsive to botulinum toxin (BTX). In addition, we systematically review the literature for cases of muscle hypertrophy associated with radiculopathy. METHODS: A 56-year-old man with a previous history of S1 root lesion presented with marked calf hypertrophy, muscle pain, cramps, fasciculations, and increased CK level. Magnetic resonance imaging and muscle biopsy confirmed true muscle hypertrophy. Electromyography (EMG) showed signs of chronic denervation-reinnervation in the right S1 myotome, with greatly increased spontaneous activity (SA) (fasciculations and complex repetitive discharges). Botox(R) was injected in 3 occasions on 4 sites on the right gastrocnemius (20U per site). Symptoms, CK level and SA on EMG (quantified) were evaluated. RESULTS: The patient improved clinically, CK level and SA steadily decreased. CONCLUSIONS: The literature review failed to identify a unique causative factor for muscle hypertrophy related to neurogenic lesions. BTX treatment was effective in our patient with muscle hypertrophy associated with SA. SIGNIFICANCE: We provide further evidence that spontaneous activity secondary to nerve lesion may cause focal muscle hypertrophy. Treatment with BTX should be considered in these conditions.

Anti-Dyskinesia Agents↗
PubMed2006

Distal excitability changes in motor axons in amyotrophic lateral sclerosis.

OBJECTIVE: Previous axonal excitability studies in amyotrophic lateral sclerosis (ALS) have suggested that impaired potassium channel function could be responsible for the generation of fasciculations, but the ectopic activity arises predominantly from the motor nerve terminals. This study tested the hypothesis that dysfunction of potassium channels is more pronounced in the more distal parts of axons. METHODS: Threshold electrotonus was used to compare accommodation at the motor point of abductor pollicis brevis, and at the wrist portion of the median nerve, between 22 patients with ALS and 19 normal subjects. As target responses for motor point stimulation, movement-related potentials were recorded using an accelerometer. RESULTS: Compared to normal subjects, ALS patients showed greater threshold changes to depolarizing conditioning currents at both the motor point and wrist, suggesting less accommodation by potassium currents. Differences in the threshold electrotonus curves between the normal and ALS groups were much more prominent at the motor point than at the wrist. CONCLUSIONS: In ALS, axonal potassium channels are impaired more prominently in distal portions of axons than at the nerve trunk, and this is consistent with evidence that fasciculations mostly arise from the nerve terminals. SIGNIFICANCE: Excitability testing at the motor point provides additional information about the pathophysiology of ALS.

Action Potentials↗
PubMed2004

Distribution of RA175/TSLC1/SynCAM, a member of the immunoglobulin superfamily, in the developing nervous system.

RA175 is a new member of the immunoglobulin superfamily with trans interaction activity, and it plays a role as a tumor suppressor in lung carcinoma (TSLC1) and as a cell adhesion molecule promoting the formation of functional synapses (SynCAM). Little is known about the biological function of RA175/TSLC1/SynCAM neural network formation during neurogenesis. We examined the distribution and colocalization of the RA175/TSLC1/SynCAM protein with other members of the immunoglobulin superfamily such as NCAM, L1, and TAG-1 in the mouse developing nervous system. Consistent with the expression of RA175/TSLC1/SynCAM mRNA, the protein was localized in the brain neuroepithelium at embryonic day (E) 9.5, neural crest at E10.5, motor neurons at E10.5, and olfactory epithelium at E16.5. In contrast with its mRNA, the protein was intensely detected on the fasciculated axons in the floor plates, ventral root, and dorsal funiculus in the E10.5-11.5 spinal cord and colocalized with NCAM and L1 on the ventral root and dorsal funiculus and partly colocalized with TAG-1 on the commissural axons and dorsal funiculus. In the E13.5-15.5 brain, RA175/TSLC1/SynCAM colocalized with NCAM and L1 on the developing thalamocortical fibers from the internal capsule (IC) and partly colocalized with TAG-1 on the cortical efferent axons in the intermediate zone (IZ). RA175/TSLC1/SynCAM was localized on the axons of some of the cortical neurons cultured in vitro. Thus, in addition to cell adhesion activity in the neuroepithelium and the synapses, RA175/TSLC1/SynCAM may be involved in neuronal migration, axon growth, pathfinding, and fasciculation on the axons of differentiating neurons.

Animals↗
PubMed2006

Nicotinic mechanisms contribute to soman-induced symptoms and lethality.

The symptoms and lethality of intoxication with the acetylcholinesterase inactivator soman are attributed primarily to excessive activation of muscarinic acetylcholine receptors; nicotinic activation is considered of less importance, a notion that may rely on studies that have used nicotinic antagonists at low doses. In this study pretreatment with the centrally acting nicotinic antagonist mecamylamine, 20mg/kg, but not 2mg/kg, prolonged survival in mice exposed to soman, 250 microg/kg (1.5 LD(50)), from 14+/-3 to 135+/-38 min (mean+/-S.E.M.; surviving animals were killed 240 min after soman administration). Pretreatment with the muscarinic blocker scopolamine, 2 or 20mg/kg (but not 0.5mg/kg) prolonged survival significantly (mean for both groups: 91 min), but the animals responded to soman with immobility, irregular respiration, fasciculation, and short episodes of convulsive crawling. These symptoms were absent in animals pretreated with scopolamine plus mecamylamine, both drugs 20mg/kg, a suggestion that they were caused by activation of nicotinic receptors. All animals pretreated with scopolamine and mecamylamine (both drugs 20 mg/kg) survived the full 240 min observation period. Administration of mecamylamine, 5 mg/kg, 5 min after soman exposure to scopolamine-pretreated animals reduced fasciculation and respiratory irregularity and prolonged survival compared to scopolamine alone, but mecamylamine, 20 mg/kg, given 10 min after soman exposure shortened survival (18+/-1 min). These results suggest that nicotinic activation plays an important part in soman-induced symptomatology and lethality but also that nicotinic antagonists given in large doses after soman exposure may have untoward effects.

Acetylcholinesterase↗
PubMed2003

Juvenile muscular atrophy of distal upper extremity associated with airway allergy: two cases successfully treated by plasma exchange.

Juvenile muscular atrophy of the distal upper extremity (JMADUE) is postulated to be a type of flexion myelopathy. However, patients with typical clinical features of JMADUE but without evidence of flexion myelopathy have been reported. We recently reported a significant association of JMADUE with airway allergy. Here we report the successful treatment by plasma exchange (PE) of two patients with both airway allergy and JMADUE without evidence of flexion myelopathy. Patient 1 had a 5-year history of allergic rhinitis and high titers of mite antigen-specific IgE, and patient 2 had an 8-year history of pollinosis and high titers of cedar pollen-specific IgE. Both patients noted progressive distal muscle atrophy and weakness of the upper extremities: patient 1 for 3 months and patient 2 for 3 years. Neurologically, both showed asymmetric intrinsic hand muscle atrophy, oblique atrophy of the forearm muscles, and weakness and contraction fasciculation (minipolymyoclonus) of these muscles without any sensory impairment. Neither had any evidence of flexion myelopathy on magnetic resonance imaging (MRI) in a flexed position. Both were subjected to PE three times. Soon after the PEs, both showed improvement of distal muscle weakness of the upper extremities and marked reduction of contraction fasciculation of the forearm muscles. Patient 1 showed marked reduction in ongoing denervation potentials in the distal muscles on needle electromyography, while patient 2 showed marked improvement of F wave persistence of bilateral median and ulnar nerves. Serum total and allergen-specific IgE decreased after PEs in both patients. PE was thus considered to be effective in these two patients having JMADUE without evidence of flexion myelopathy. These observations may suggest the involvement of an immune-mediated process in the neural damage of JMADUE without evidence of flexion myelopathy, especially in patients with atopic diathesis, and may support the notion that JMADUE is etiologically heterogeneous.

Adolescent↗
PubMed2001

Substrate-bound human recombinant L1 selectively promotes neuronal attachment and outgrowth in the presence of astrocytes and fibroblasts.

Axonal pathfinding is a complex process that is mediated through cell-matrix and cell-cell interactions. A large number of studies have demonstrated that ECM and ECM-derived proteins and peptides are potent promoters of neurite outgrowth, however much less attention is given to the fact that these same ligands also elicit responses in a wide variety of non-neuronal cell types. We examined the use of a substrate-bound recombinant form of human L1, an integral membrane protein, as a ligand for bridging materials for repairing the CNS by studying its effectiveness in promoting specific responses of neuronal cells in the presence of astrocytes and fibroblasts. L1, a cell adhesion molecule expressed in the developing CNS and PNS, has strong neurite promoting activity, and contributes to axonal guidance and axonal fasciculation during development. In this study, substrates treated with L1-Fc were compared to subtrates treated with fibronectin and poly-lysine (PDL) with respect to their interaction with a variety of cell types, including three types of neurons (DRG neurons, cerebellar granule neurons, and hippocampal neurons), astrocytes, dermal fibroblasts, and meningeal cells. L1-Fc-treated substrates supported significantly higher levels of neurite outgrowth relative to fibronectin and PDL, while inhibiting the attachment of astrocytes, meningeal cells, and fibroblasts. We also show that neuronal cells attach to and extend neurites on 30 microm diameter L1-Fc-treated filaments as an example of a potentially useful bridging substrate. The high level of biological specificity displayed by surface-bound L1, along with the fact that it is a potent promoter of neurite outgrowth, is normally expressed on axons and regulates axonal fasciculation during normal development bodes well for its use on bridging materials for the repair of the CNS, and suggests that cell adhesion molecules, in general, may be useful for biomaterial modification. Moreover, small diameter filaments coated with L1-Fc may function in an analogous way to pioneering axons that guide the growth of axons to distal targets during development.

Animals↗
PubMed1993

Culture of isolated embryonic chick dorsal root ganglia at an air-liquid interface: a simple method for studying the mechanism and control of neurite outgrowth.

Extensive neurite outgrowth occurs within 24 h from explants of embryonic chick dorsal root ganglia floated on the surface of serum-free culture medium. The amount of neurite outgrowth was less in culture medium containing serum albumen and varied systematically with the concentration of nerve growth factor (NGF). Compared with outgrowth from floating ganglia, the NGF-dependent outgrowth of neurites from ganglia stuck to coated substrata was much less on polylysine, but outgrowth was more extensive on a laminin-coated substrate. Neurites growing out from floating ganglia showed more fasciculation than those growing out from adherent ganglia. This new, simple preparation provides a serum- and substrate-independent system for studying mechanisms of neurite outgrowth and for quantitative bioassay for potential neurotrophic factors or for factors which influence neurite fasciculation.

Animals↗
PubMed1999

A rapid method for semi-quantitative analysis of neurite outgrowth from chick DRG explants using image analysis.

Neurite outgrowth from dorsal root ganglion (DRG) explants is a method of evaluating neurotrophic activity of growth factors and neurotrophin mimetics. The drawbacks to this approach are the difficulties in quantifying the response. Neurite counts are time consuming and labour intensive, and the accuracy is often questionable due to branching and fasciculation of the neurites. We report here a method of semi-quantitative analysis of neurite outgrowth from chick DRG explants, using image analysis to quantify the area occupied by neurites emanating from the ganglion. This method is rapid, takes into account both the length and number of neurites, and is unaffected by neurite fasciculation or branching. Primary explants of chick DRGs were treated with the neurotrophins nerve growth factor (NGF) or neurotrophin-3 (NT-3) and with the compound K252a. K252b was tested for potentiation of the response to NT-3. The results show a dose dependent outgrowth of neurites from explants treated with NGF, NT-3 and K252a, and potentiation of the NT-3 response by K252b. These responses were quantified by neurite area quantification using image analysis. We conclude that neurite area measurement using image analysis provides a robust means of evaluating neurotrophic activity of growth factors and neurotrophin mimetics in vitro.

Animals↗
PubMed2000

Lower motor neuron disease associated with myelofibrosis.

We present a patient who has signs pointing to the involvement of lower motor neurons and myelofibrosis. To our knowledge, unlike lymphoproliferative disorders, co-occurrence of myelofibrosis and lower motor neuron disease (MND) has not been reported so far. A 64-year-old male patient was admitted to our hospital with the complaint of painful cramps in his neck and forearms. On physical examination marked hepatomegaly and splenomegaly were found. On neurologic examination nasal quality of the voice and slight palatal weakness were detected. There were generalised slight weakness and atrophy in both proximal and distal muscle groups. Fasciculations were observed especially in forearm muscles and it was observed that he had been avoiding head movements because of painful muscle cramps. Deep tendon reflexes were hypoactive. Nerve conduction studies were normal. By needle electromyography, giant motor unit action potentials (amplitudes up to 8 mV), fibrillation potentials, positive sharp waves and fasciculation potentials were detected in all muscles which were investigated. A hypercellular bone marrow (100%) was determined by bone marrow biopsy. In addition to increased production of the myeloid and megakaryocytic lines, abnormal aggregation and grouping of megakaryocytes were seen. Reticular fibers were increased. He had some benefit of dyphenilhydantoin treatment given for the painful cramps in his neck and forearm muscles. Hydroxyurea treatment was started for myelofibrosis. Six months later, his general condition was better, and the painful cramps were completely resolved. No marked deterioration has been detected in neurologic examination and electromyography for 1 year.

Atrophy↗
PubMed1998

Multiple roles of neural cell adhesion molecule, neural cell adhesion molecule-polysialic acid, and L1 adhesion molecules during sensory innervation of the otic epithelium in vitro.

To explore the role of cell adhesion molecules in the innervation of the inner ear, antibody perturbation was used on histotypic co-cultures of the ganglionic and epithelial anlagen derived from the otocyst. When unperturbed, these tissues survived and differentiated in this culture system with outgrowth of fasciculated neuronal fibers which expressed neural cell adhesion molecule and L1. The fibers exhibited target choice and penetration, then branching and spreading within the otic epithelium as individual axons. Treatment of the co-cultures, or of the ganglionic anlagen alone, with anti-neural cell adhesion molecule or anti-L1 Fab fragments produced a defasciculation of fibers but did not affect neurite outgrowth. In the co-cultures this defasciculation was accompanied by a small increase in the number of fibers found in inappropriate tissues. However, the antibodies did not prevent fiber entry to the otic epithelium. In contrast, removal of polysialic acid from neural cell adhesion molecule with endoneuraminadase-N, while producing a similar fiber defasciculation, also increased the incidence of fibers entering the epithelium. Nevertheless, once within the target tissue, the individual fibers responded to either Fab or to desialylation by spreading out more rapidly, branching, and growing farther into the epithelium. The findings suggest that fasciculation is not essential for specific sensory fibers to seek out and penetrate the appropriate target, although it may improve their tracking efficiency. Polysialic acid on neural cell adhesion molecule appears to limit initial penetration of the target epithelium. Polysialic acid as well as neural cell adhesion molecule and L1 function are involved in fiber-target interactions that influence the arborization of sensory axons within the otic epithelium.

Animals↗
PubMed1999

Combinatorial expression of cadherins in the tectum and the sorting of neurites in the tectofugal pathways of the chicken embryo.

The expression of four cadherins (N-cadherin, R-cadherin, cadherin-6B and cadherin-7) was mapped in the developing tectal system of the chicken embryo from four to 19 days of incubation. Each of the cadherins is expressed in a restricted fashion in specific tectal layers, with partial overlap between the cadherins. In some layers, subpopulations of neurons differentially express the cadherins, e.g., in the stratum griseum centrale. Double labeling demonstrates that many of the projection neurons in this layer co-express at least two cadherins. Fibers of the efferent (tectofugal) pathways originating in these neurons also differentially express the cadherins, most prominently at around 1 1 days of incubation. While the different subpopulations of cadherin-expressing projection neurons are dispersed and mixed within the tectum, their neurites sort out and fasciculate according to which cadherin they express, as they collect in the major output of the tectum, the brachium colliculi superioris. From here, cadherin-expressing fascicles follow separate paths to their respective target areas, some of which also express the respective cadherins, in a matching fashion. We propose that the preferentially homophilic binding of cadherins provides a potential adhesive basis for the sorting and selective fasciculation of specific subpopulations of neurites, similar to the well-established sorting and aggregation of cells expressing cadherins. The combinatorial expression of cadherins by the tectal projection neurons may contribute to the complexity and specificity of functional connections in this system.

Animals↗
PubMed1997

The gene of the neural cell recognition molecule F11: conserved exon-intron arrangement in genes of neural members of the immunoglobulin superfamily.

The chicken neural glycoprotein F11 is a cell recognition molecule implicated in neurohistogenesis, in particular in the context of neurite outgrowth and fasciculation. F11 is a glycosyl-phosphatidylinositol-linked member of the immunoglobulin superfamily that is also termed contactin or F3 in humans and rodents, respectively. In this study, we report the complete structure of the F11 gene. It is composed of 23 exons distributed over more than 100 kb of genomic DNA and each of the ten domains of the F11 protein is encoded by two exons. The sizes of the introns vary by two orders of magnitude ranging from 150 bp to more than 15 kb. All interdomain introns are in phase one, i.e. are inserted after the first nucleotide of a codon, being consistent with assembly of a F11 progenitor gene via exon shuffling. The intradomain introns are localized at variable sites within the domains and have different intron phases. This study reveals a remarkable similarity of the F11 gene with the gene of axonin-1, a related neural immunoglobulin superfamily member which is also implicated in neurite outgrowth and fasciculation. The intron positions with respect to the protein domain organization are found to be identical, strongly suggesting that both genes are derived from a common ancestor that already had this exon-intron structure.

Animals↗
PubMed2001

Intercostal nerve transfer classification.

We report a new classification of intercostal nerve transfer. The specific application in brachial plexus reconstruction is described. This method was applied in intercostal nerve transfer to the musculocutaneous nerve in 15 patients. In type 1, "MOTOR to MIXED" transfer one harvest only the intercostal main motor branch which is connected at the trunk of the musculocutaneous nerve, without fascicular specificity. In type 2, "MIXED to MIXED" transfer, based on neural cartography, the main motor branch and its sensitive accessory anterior branches are connected to the musculocutaneous nerve trunk, in attempt to connect the motor fascicules together at the center and also the sensory fascicules together, at the circumference. In type 3, "MOTOR to MOTOR" transfer, the intercostal main motor branch is connected to the musculocutaneous motor branch directly destined to the biceps brachialis. The aim of this work is to evaluate the results between different series.

Brachial Plexus↗
PubMed2005

Caespitotheca gen. nov., an ancestral genus in the Erysiphales.

The phylogenetic position of Uncinula forestalis within the Erysiphales has been inferred from 5.8S, 18S, and 28S rDNA sequences. Although the appendages of the ascomata are Uncinula-like, i.e. unbranched with curved-coiled apices, U. forestalis is situated at the very base of the large Erysiphales cluster, far from the 'Pseudoidium' clade (Erysiphe, including Microsphaera and Uncinula) and separate from the recently introduced basal genus Parauncinula. U. forestalis differs morphologically from the species of Erysiphe sect. Uncinula in having terminal, fasciculate (as in Podosphaera tridactyla), septate ascoma appendages and a Euoidium-like anamorph (conidia catenate). In Parauncinula, the appendages are also terminal but not fasciculate, the ascospores are curved, and the anamorph is lacking. Uncinula forestalis is a basal, tree-inhabiting powdery mildew with some additional ancestral characteristics, including Uncinula-like appendages and 6-8-spored asci. The new genus Caespitotheca gen. nov. is described with C. forestalis comb. nov. (syn. Uncinula forestalis) as the type species. We calculated the timing of the divergence of U. forestalis and P. septata using a molecular clock of the Erysiphales (6.5 x 10-10 changes per site per year in domains D1 and D2 of 28S rDNA) and a 28S rDNA data set. The results suggest that the divergence of U. forestalis and P. septata from other Ervsiphales occurred between 90 and 80 Myr ago; i.e. the divergence of the two ancestral species may have occurred in the late Cretaceous.

Ascomycota↗
PubMed2003

Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth.

Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation that segregated with schizophrenia in a Scottish family. Predicted DISC1 product has no significant homology to other known proteins. Here, we demonstrated the existence of DISC1 protein and identified fasciculation and elongation protein zeta-1 (FEZ1) as an interacting partner of DISC1 by a yeast two-hybrid study. FEZ1 and its nematode homolog are reported to represent a new protein family involved in axonal outgrowth and fasciculation. In cultured hippocampal neurons, DISC1 and FEZ1 colocalized in growth cones. Interactions of these proteins were associated with F-actin. In the course of neuronal differentiation of PC12 cells, upregulation of DISC1/FEZ1 interaction was observed as along with enhanced extension of neurites by overexpression of DISC1. The present study shows that DISC1 participates in neurite outgrowth through its interaction with FEZ1. Recent studies have provided reliable evidence that schizophrenia is a neurodevelopmental disorder. As there is a high level of DISC1 expression in developing rat brain, dysfunction of DISC1 may confer susceptibility to psychiatric illnesses through abnormal development of the nervous system.

Actins↗
PubMed1999

Neuronal pathfinding during development of the rostral brain in Xenopus.

1. The aim of the present study is to define the trajectory of growing axons as well as to characterize guidance cues mediating neuronal pathfinding in the rostral brain of embryonic Xenopus. 2. The early embryonic Xenopus brain consists of a stereotypical pattern of axon tracts arranged about orthogonal axes. This scaffold of axons is constructed around the tracts of the postoptic commissure (TPOC), a pair of longitudinal tracts that course along the ventrolateral surface of the brain. These tracts are connected across the midline by two commissures. Three short tracts join the dorsal brain to the TPOC. 3. The TPOC consists of chemically distinct subpopulations of axons defined by the expression of NOC, novel glycoforms of the neural cell adhesion molecule N-CAM. Axons expressing NOC-2 sort out in the ventral portion of the TPOC. NOC-2+ axons in the supraoptic tract appear to fasciculate with axons expressing the same cell adhesion molecule in the ventral TPOC. 4. Chondroitin sulphates modulate the growth of axons from the TPOC into the ventral tegmental commissural pathway in the rostral midbrain. 5. Unique guidance cues are responsible for neuronal pathfinding at specific points in the trajectory of growing axons in the rostral brain. We have shown that selective fasciculation mediates the turning of axons into the major longitudinal tract, while specific cues are required for axons to exit this pathway.

Animals↗
PubMed1998

The pachygyria-polymicrogyria spectrum of cortical dysplasia in X-linked hydrocephalus.

Neural cell adhesion molecules (CAM) play important roles in neural development, neurite outgrowth, axonal guidance, fasciculation and synapse formation. Neuropathological studies of X-linked hydrocephalus (XLH) associated with L1 CAM mutations emphasize marked hypoplasia of the pyramidal tract, agenesis of the corpus callosum and septum pellucidum, and a thin cerebral mantle with hypoplastic white matter, but there are no detailed studies of the cerebral cortex in the literature. We report clinical, neuroimaging, and neuropathological findings in three boys with XLH. All had severe congenital hydrocephalus with marked thinning of the cerebral mantle and severe development disabilities. The brain specimens from the three boys showed both pachygyria and polymicrogyria, hypoplasia of the medullary pyramids, hypoplasia of the corpus callosum, small anterior commissure, hypoplasia and poorly differentiated hippocampi. A small but patent aqueduct was present in all three brains. Despite the extensive cerebral malformations, the cortex in all three brains showed normal-appearing laminar cortical neuronal architecture and absence of gliosis. In XLH, it is likely that the poor developmental outcome of spasticity, contractures and severe mental retardation results from a disturbance of neuronal connectivity, fasciculation, and synapse formation rather than aqueductal stenosis, increased intracranial pressure, or abnormal neuroblast migration.

Antigens, Surface↗