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J Dodd

Publications and source records attributed to J Dodd.

At least 55 records · Page 3Linked to original sources
PubMed1991

Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate.

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.

Animals↗
PubMed1990

Mesodermal control of neural cell identity: floor plate induction by the notochord.

The floor plate is a specialized group of midline neuroepithelial cells that appears to regulate cell differentiation and axonal growth in the developing vertebrate nervous system. A floor plate-specific chemoattractant was used as a marker to examine the role of the notochord in avian floor plate development. Expression of this chemoattractant in lateral cells of the neural plate and neural tube was induced by an ectopic notochord, and midline neural tube cells did not express the chemoattractant after removal of the notochord early in development. These results provide evidence that a local signal from the notochord induces the functional properties of the floor plate.

Animals↗
PubMed1990

The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity.

Pathfinding of axons in the developing nervous system is thought to be mediated by glycoproteins expressed on the surface of embryonic axons and growth cones. One molecule suggested to play a role in axonal growth is TAG-1, a 135 kd glycoprotein expressed transiently on the surface of subsets of neurons in the developing mammalian nervous system. We isolated a full-length cDNA clone encoding rat TAG-1. TAG-1 has six immunoglobulin-like domains and four fibronectin type III-like repeats and is structurally similar to other immunoglobulin-like proteins expressed on developing axons. Neurons maintained in vitro on a substrate of TAG-1 extend long neurites, suggesting that this protein plays a role in the initial growth and guidance of axons in vivo. TAG-1 is anchored to the neuronal membrane via a glycosyl phosphatidylinositol linkage and is also released from neurons, suggesting that TAG-1 also functions as a substrate adhesion molecule when released into the extracellular environment.

Amino Acid Sequence↗
PubMed1990

The moral reasoning of juvenile delinquents: a meta-analysis.

To test the hypothesized immaturity of juvenile delinquents' moral reasoning, the results of 15 studies of the moral reasoning of juvenile delinquents were integrated quantitatively using meta-analysis. Hedges and Olkin (1985) methods were used to (a) compute effect sizes, (b) test the homogeneity of the obtained effect sizes, and (c) test the statistical significance of the pooled mean effect size. The results supported the hypothesis that the moral reasoning of juvenile delinquents is immature. It was concluded that several other issues are in need of investigation.

Adolescent↗
PubMed1990

Identification of electrophysiologically distinct subpopulations of rat taste cells.

The gustatory sensory system provides animals with a rapid chemical analysis of a potential food substance providing information necessary to facilitate ingestion or rejection of the food. The process of gustatory transduction is initiated in the taste cells in the lingual epithelium. However, due to the small size, scarcity of the cells and their location, embedded in a keratinized squamous epithelium, it has been difficult to study the primary events in the transduction process. Recently, we have developed a preparation of dissociated rat taste cells that permits studies of the taste transduction process in single isolated cells. We have now investigated the electrophysiological properties of the rat taste cells using the patch-clamp technique. We have identified two populations of cells within the taste bud: one expressing a voltage-dependent potassium current and the second containing both voltage-dependent sodium and potassium currents. The potassium current in both cell groups is blocked by external TEA, Ba2+, and quinine. Two types of K+ channels have been identified: a 90-pS delayed rectifier K+ channel and a "maxi" calcium-activated K+ channel. The sodium current is blocked by TTX, but not by amiloride.

Animals↗
PubMed1990

Monoclonal antibodies against sensory neuron specific antigens define the extent of neuronal abnormality in the mf mutant rat.

The mutant rat mutilated foot (mf) is affected by a sensory neuropathy which does not involve the parts of the body innervated by the thoracic cord. The possibility that sensory cells subserving clinically normal regions may be functionally spared by the mutation has been investigated by studying the expression of cell surface oligosaccharides by dorsal root ganglia (DRG) and their central processes in the spinal cord. The study included 3 lactoseries epitopes (TC6, LD2 and LA4) and the globoseries epitope SSEA3. The results show that at cervical and lumbar levels in mf rats there are reduced numbers of DRG cells reacting with the various antibodies and less immunostaining in the dorsal horns. The unexpected finding that thoracic ganglia and cord share similar appearances suggests that, in spite of being normal in number and able to produce normal amounts of substance P, thoracic DRG cells in mf rats take part in the mutation as shown by their inability to produce normal amounts of oligosaccharides and to transport them to the axon terminals.

Animals↗
PubMed1990

Conditional expression of RPA190, the gene encoding the largest subunit of yeast RNA polymerase I: effects of decreased rRNA synthesis on ribosomal protein synthesis.

The synthesis of ribosomal proteins (r proteins) under the conditions of greatly reduced RNA synthesis were studied by using a strain of the yeast Saccharomyces cerevisiae in which the production of the largest subunit (RPA190) of RNA polymerase I was controlled by the galactose promoter. Although growth on galactose medium was normal, the strain was unable to sustain growth when shifted to glucose medium. This growth defect was shown to be due to a preferential decrease in RNA synthesis caused by deprivation of RNA polymerase I. Under these conditions, the accumulation of r proteins decreased to match the rRNA synthesis rate. When proteins were pulse-labeled for short periods, no or only a weak decrease was observed in the differential synthesis rate of several r proteins (L5, L39, L29 and/or L28, L27 and/or S21) relative to those of control cells synthesizing RPA190 from the normal promoter. Degradation of these r proteins synthesized in excess was observed during subsequent chase periods. Analysis of the amounts of mRNAs for L3 and L29 and their locations in polysomes also suggested that the synthesis of these proteins relative to other cellular proteins were comparable to those observed in control cells. However, Northern analysis of several r-protein mRNAs revealed that the unspliced precursor mRNA for r-protein L32 accumulated when rRNA synthesis rates were decreased. This result supports the feedback regulation model in which excess L32 protein inhibits the splicing of its own precursor mRNA, as proposed by previous workers (M. D. Dabeva, M. A. Post-Beittenmiller, and J. R. Warner, Proc. Natl. Acad. Sci. USA 83:5854-5857, 1986).

Base Sequence↗
PubMed1990

Guidance of commissural growth cones at the floor plate in embryonic rat spinal cord.

The floor plate of the embryonic rat spinal cord has been proposed to act as an intermediate target that plays a role in the pattern of extension of commissural axons. To begin to examine the role of the floor plate in axon guidance at the midline, we have studied the precision of the commissural axon projection to and across the floor plate during development. To delineate the pathway, the fluorescent carbocyanine dye, Di-I, has been used as a probe. We show that commissural axons traverse the floor plate and turn rostrally at its contralateral border with remarkable precision. Axons were not observed to turn ipsilaterally and turned only upon reaching the contralateral edge of the floor plate. Virtually all commissural axons follow this route. The morphology of commissural growth cones was also examined. As they encountered the floor plate, commissural growth cones became larger and increased in complexity. The reorientation of axons in register with the floor plate boundary and the change in the morphological properties of commissural growth cones as they traverse the midline suggest that the floor plate may act as a guidepost with functions similar to cells that have been implicated in axon guidance in invertebrates.

Animals↗
PubMed1990

Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant.

Developing axons are guided to their targets by molecular cues in their local environment. Some cues are short-range, deriving from cells along axonal pathways. There is also increasing evidence for longer-range guidance cues, in the form of gradients of diffusible chemoattractant molecules, which originate from restricted populations of target cells. The guidance of developing commissural axons within the spinal cord depends on one of their intermediate cellular targets, the floor plate. We have shown previously that floor plate cells secrete a diffusible factor(s) that can alter the direction of commissural axon growth in vitro. Here we show that the factor is an effective chemoattractant for commissural axons. It can diffuse considerable distances through a collagen gel matrix and through dorsal and ventral neural epithelium in vitro to reorient the growth of virtually all commissural axons. The orientation of axons occurs in the absence of detectable effects on the survival of commissural neurons or on the rate of commissural axon extension. The regionally restricted expression of the factor suggests that it is present in the embryonic spinal cord in a gradient with its high point at the floor plate. These observations support the idea that the guidance of commissural axons to the ventral midline of the spinal cord results in part from the secretion of a chemoattractant by the floor plate.

Animals↗
PubMed1989

Identification of alpha-galactose (alpha-fucose)-asialo-GM1 glycolipid expressed by subsets of rat dorsal root ganglion neurons.

Distinct cell-surface glycoconjugates are expressed on specific subsets of dorsal root ganglion (DRG) neurons and DRG terminals projecting to the superficial dorsal horn of rat spinal cord (Dodd, J., and Jessell, T. M. (1985) J. Neurosci. 5, 3278-3294). Carbohydrate antigens detected by monoclonal antibodies (mAbs) TC6, KH10, and LD2 are restricted to about 20% of DRG neurons projecting to lamina IIB (dorsal), whereas antigens recognized by mAb LA4 are expressed by about 50% of DRG neurons projecting to lamina IIB (ventral). These mAbs were generated against rat pancreatic acinar cell line AR4-2J antigens. The glycolipid antigens in AR4-2J cells reacting with these mAbs have been structurally characterized by sequential hydrolysis with various exoglycosidases, immunochemical tests, linkage analysis of permethylated alditol acetates, capillary gas liquid chromatography-mass spectrometry, mass spectrometry of permethylated compounds, and by fast atom bombardment mass spectrometry of the native antigens. The structure of the major antigen (IA) in AR4-2J cells was determined to be: (formula; see text) The asialo derivative of IA and the novel disialo form of IA (Gal alpha 1----3(Fuc alpha 1----2)----GD1b) have been also identified. The DRG neurons contained only the neutral glycolipid, asialo form of IA. All these antigens reacted equivalently in the high performance thin layer chromatography-immuno overlay assay with the TC6, LD2, and LA4 mAbs. The molecular specificity of the three mAbs was determined by rection with a variety of possible antigens and appears to be the same. All three mAbs required terminal Gal alpha 1----3(Fuc alpha 1----2)Gal beta 1----3GalNAc (or 4GlcNAc) for full reactivity. Only partial reactivity was observed with compounds in which alpha-Fuc was removed. The observed restricted reactivity of mAbs TC6, LD2, and LA4 in subsets of DRG neurons and in ventral and dorsal areas of lamina IIB may be due to different topographical expression of the antigen in the neuronal membrane.

Animals↗
PubMed1989

Polarity and patterning in the neural tube: the origin and function of the floor plate.

Little is known about the cellular and molecular mechanisms that determine neuronal cell fate and the patterning of neuronal connections in the vertebrate central nervous system. In this paper we summarize evidence which indicates that some aspects of neuronal differentiation and axon guidance are regulated by specialized epithelial cells that occupy the medial region of the neural plate and, later, the ventral midline of the spinal cord. This cell group, termed the notoplate/floor plate appears to constitute a distinct compartment within the neural plate that is more closely related in lineage and perhaps also in function to axial mesodermal cells of the underlying notochord than to other neural plate cells. Cells of the notoplate exhibit specialized mechanical and adhesive properties that may contribute to neurulation. At later stages of development, the floor plate appears to guide developing axons in the embryonic spinal cord by releasing a diffusible chemoattractant factor and by virtue of its specialized cell surface properties. The floor plate may also play a role in the determination of cell identity and patterning at earlier stages of neural tube development.

Animals↗
PubMed1989

Carbohydrate recognition in neuronal development: structure and expression of surface oligosaccharides and beta-galactoside-binding lectins.

The differentiation and development of vertebrate neurons is controlled in part by interactions with cell surface and extracellular matrix molecules, many of which are glycoproteins that mediate their developmental actions by homophilic or heterophilic binding to other glycoproteins. In addition there is increasing evidence that cell recognition and adhesion in some embryonic cell types involve interactions between cell surface oligosaccharides and complementary carbohydrate-binding proteins. Although a role for carbohydrate recognition in neuronal development has been proposed, the precise function of complex carbohydrate structures on neural cells has not been defined. To approach this problem, we have examined the structure and expression of cell surface oligosaccharides and carbohydrate-binding proteins by primary sensory neurons in the rat dorsal root ganglion (DRG). There are several functionally distinct subsets of DRG neurons, each of which conveys a different sensory modality to distinct target domains in the spinal cord. Monoclonal antibodies against defined oligosaccharide structures identify each of the major subsets of DRG neurons on the basis of their expression of a distinct set of complex oligosaccharides, derived from lacto-, globo- and ganglioseries backbone structures. In particular, small diameter DRG neurons involved in pain processing express beta-galactoside-based lactoseries oligosaccharides. DRG and spinal cord neurons also express two soluble beta-galactoside-binding proteins of relative molecular masses 14,500 and 29,000, termed RL-14.5 and RL-29, which represent potential ligands for lactoseries oligosaccharides. RL-14.5 is expressed by the majority of DRG neurons whereas RL-29 is restricted to the subset of small DRG neurons that express surface N-acetyllactosamine structures. RL-14.5 and RL-29 are expressed soon after the differentiation of DRG neurons and appear to be released from cultured DRG neurons. Rat brain cDNA clones encoding RL-14.5 have been isolated. The nucleotide and predicted amino acid sequence of RL-14.5 has confirmed that this lectin is highly homologous to soluble beta-galactoside-binding proteins in other vertebrate species. Northern blot analysis and in situ hybridization indicate that RL-14.5 mRNA is selectively expressed in sensory and motor neurons in the rat nervous system. The selective expression of lactoseries oligosaccharides and complementary beta-galactoside-binding lectins may contribute to the differentiation and/or development of these two classes of neurons.

Aging↗
PubMed1989

Morphology and distribution of primary afferent fibres expressing alpha-galactose extended oligosaccharides in the spinal cord and brainstem of the rat. Light microscopy.

The light microscopic morphology and distribution of non-substance P-containing small primary afferent fibres were studied. These fibres were labelled using LD2 and LA4 monoclonal antibodies which recognize alpha-galactose extended oligosaccharides expressed by primary afferent neurons. The LD2 and LA4 antibodies immunostained small primary afferent fibres ending mainly in lamina II of the spinal cord dorsal horn and trigeminal subnucleus caudalis of the rat. The lamination pattern of both types of primary afferents was assessed using an image analysis system. The highest density of LD2-immunoreactive fibres was located in a patchy band located in lamina II outer, while LA4-immunoreactive fibres were distributed mainly through lamina II inner. In lateral regions of cervical and lumbar dorsal horn the LA4-immunoreactive band is broader and comprises almost all lamina II. In contrast to substance P-containing primary afferents, a low density of LD2- or LA4-immunoreactive fibres was found in lamina I, and no terminal fields were found in lamina V or lamina X of the spinal cord or in levels of the trigeminal system outside the subnucleus caudalis. Both antibodies also labelled the parent fibres in the white matter fasciles. LD2-immunoreactive fibres were located in the dorsal roots, medial regions of the Lissauer tract, dorsal columns of the spinal cord, outer regions of the spinal trigeminal tract and dorsal to the cuneatus and gracilis nuclei. In contrast, LA4-immunoreactive fibres were restricted to the dorsal roots, medial and lateral regions of the Lissauer tract and the outer regions of the trigeminal tract. Immunostained fibres in the rootlets of the X and IX nerves and immunoreactive terminal arborizations in various subnuclei of the nucleus tractus solitarius were seen using both antibodies. These results show that subpopulations of small primary afferents stained by LD2 and LA4 antibodies have distinct patterns of central distribution and are consistent with a subdivision of small primary afferents into peptide- and non-peptide-containing groups.

Animals↗
PubMed1989

Ultrastructure of primary afferent fibres and terminals expressing alpha-galactose extended oligosaccharides in the spinal cord and brainstem of the rat.

The ultrastructural characteristics of primary afferent fibres, which express alpha-galactose extended oligosaccharides recognized by LD2 and LA4 monoclonal antibodies, and the subcellular localization of these oligosaccharides were studied. LD2 and LA4 antibodies both label intensely the plasma membrane of primary afferent fibres, and with LD2 antibody all immunoreactive profiles also possessed strong intracellular staining. In contrast, intracellular staining with LA4 antibody was observed in only a subpopulation of stained profiles. LD2-immunoreactive fibres were detected in trigeminal and Lissauer tracts and in lamina I (LI) and lamina II (LII), and appeared as a mixture of unmyelinated and myelinated fibres. The highest density of LD2-immunoreactive synaptic boutons was found in lamina II outer (LIIo). Many of the terminals were simple dome-shaped terminals, making single asymmetric synapses over small and medium-sized dendritic shafts and dendritic spines. All LA4-immunoreactive fibres were unmyelinated. In addition, some small scalloped central-glomerular terminals contacting two or three dendrites were found. LA4-immunoreactive fibres were found more frequently than terminals and appeared most heavily immunostained in trigeminal and Lissauer tracts. In the neuropil of LI and LII, LA4 profiles were generally very weakly immunostained, although a small sample of immunostained synaptic boutons was detected. All LA4-immunoreactive terminals were found in lamina II inner (LIIi) and made simple asymmetric axodendritic synapses. In addition to axons and terminals, some dendrites exhibited LD2 immunoreactivity and this was most intense in the region of synaptic vesicles. In addition to neurons, some endothelial cells were immunostained with LD2 antibody and astrocytes were immunostained with LA4 antibody.

Animals↗
PubMed1988

A bitter substance induces a rise in intracellular calcium in a subpopulation of rat taste cells.

The sense of taste permits animals to discriminate between foods that are safe and those that are toxic. Because most poisonous plant alkaloids are intensely bitter, bitter taste warns animals of potentially hazardous foods. To investigate the mechanism of bitter taste transduction, a preparation of dissociated rat taste cells was developed that can be studied with techniques designed for single-cell measurements. Denatonium, a very bitter substance, caused a rise in the intracellular calcium concentration due to release from internal stores in a small subpopulation of taste cells. Thus, the transduction of bitter taste may occur via a receptor-second messenger mechanism leading to neurotransmitter release and may not involve depolarization-mediated calcium entry.

Animals↗
PubMed1988

Axon guidance and the patterning of neuronal projections in vertebrates.

Over the past decade, new insights have been obtained into the cellular strategies and molecular mechanisms that guide axons to their targets in the developing vertebrate nervous system. Axons select pathways by recognizing specific cues in their environment. These cues include cell surface and extracellular matrix molecules that mediate cell and substrate adhesion and axon fasciculation, molecules with contact-dependent inhibitory properties, and diffusible tropic factors. Several guidance cues may operate in a coordinated way to generate the distinct axonal trajectories of individual neurons.

Animals↗