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C Redies

Publications and source records attributed to C Redies.

At least 19 recordsLinked to original sources
PubMed1995

Cadherin expression in the developing vertebrate CNS: from neuromeres to brain nuclei and neural circuits.

Cadherins are a family of cell surface glycoproteins which mediate cell-cell adhesion by a Ca(2+)-dependent mechanism. Results from in vitro studies with cadherin-transfected cell lines show that cadherins preferentially bind to each other in a homophilic fashion. In the developing vertebrate brain, at least 10 cadherins are found. Some of these cadherins are expressed in a restricted fashion in particular developing brain nuclei and neural circuits. Based on these results, specific morphogenetic roles for cadherins during CNS development have been proposed. This review focuses on the possible role of cadherin-mediated sorting and aggregation of early neurons and neurites in the formation of brain nuclei, fiber tracts, and neural circuits. Moreover, at least 1 cadherin is also expressed in a segmental ("neuromeric") fashion in the early chicken forebrain, suggesting that this cadherin regulates developmental processes involved in the transformation from the neuromeric organization of the early neuroepithelium to the functional organization of the mature brain.

Animals↗
PubMed1995

R-cadherin expression during nucleus formation in chicken forebrain neuromeres.

The primordial neuroepithelium of the vertebrate forebrain consists of transverse and longitudinal morphogenetic compartments ("neuromeres"). During development, neurons born in the ventricular zone of each neuromere migrate outward to the mantle zone. Here, neuroblasts gradually accumulate and aggregate either into sheets ("laminae") or into roundish structures ("nuclei"). As brain architecture matures, sets of nuclei and laminae derived from several neuromeres become connected by fiber tracts to form functional circuits. We show by immunostaining and in situ hybridization techniques that, in the E3-E5 chicken embryo, the cell adhesion molecule R-cadherin is expressed in several stripes and patches in the forebrain neuroepithelium. This expression pattern reflects, at least in part, the neuromeric organization of the forebrain. For example, in both the ventral and dorsal thalamus, R-cadherin expression has a sharp border at the respective caudal neuromere boundary. Moreover, focusing on the mid-hypothalamic region, we demonstrate that a subset of postmitotic neuroblasts in the ventricular zone express R-cadherin during their migration to the mantle zone, where they aggregate into particular nuclei. In the mantle zone, R-cadherin-expressing neuroblasts accumulate in parallel with neuroblasts expressing another cadherin, N-cadherin. The two types of cells segregate from each other to form adjacent nuclei. Some of the R- and the N-cadherin-positive nuclei form parts of particular functional circuits in the mature brain. In conclusion, our results suggest that cadherins play a role in the formation of brain nuclei and in the developmental transformation from neuromeric to functional organization in the vertebrate forebrain.

Animals↗
PubMed1994

Similarities in structure and expression between mouse P-cadherin, chicken B-cadherin and frog XB/U-cadherin.

By immunological methods, we show that the monoclonal antibody 6D5 which reacts specifically with Xenopus laevis XB/U-cadherin, also binds to mouse P-cadherin and to chicken B-cadherin but not to the respective E-cadherins (L-CAM) or other "classical" cadherins in these species. In the first extracellular domain, three amino acid residues are identified that are shared by frog XB/U-cadherin, chicken B-cadherin and mammalian P-cadherins but not by the other "classical" cadherins. With few exceptions, the other cadherins possess residues at these positions that are also characteristic of each type of cadherin. Moreover, the expression patterns of P-, B-, and XB/U-cadherin in mouse, chicken and frog are more similar to each other than they are to those of the E-cadherins, L-CAM or other classical cadherins. Taken together, our results suggest that mammalian P-cadherins, chicken B-cadherin and frog XB/U-cadherin are closely related, if not homologous, molecules. A number of differences in the expression patterns between P-, B-, and XB/U-cadherin indicate that these molecules assume differential morphogenetic roles in different species.

Amino Acid Sequence↗
PubMed1993

Differential expression of N- and R-cadherin in functional neuronal systems and other structures of the developing chicken brain.

Cadherins are a family of cell surface molecules mediating calcium-dependent cell-cell adhesion in a variety of tissues. More than a dozen cadherins are expressed in the vertebrate brain. To obtain insight into the biological significance of this diversity in cadherin expression, we mapped the expression of N- and R-cadherin in the brain of the developing chicken embryo (days 2-19 of incubation) by immunohistochemical and in situ hybridization techniques. Whereas the expression of N- and R-cadherin is relatively uniform or weak in early (about 2-5 days of incubation) and late development (15 days of incubation to hatching stage), these two molecules are differentially expressed in specific nuclei and fiber tracts between days 6-11 of incubation. For example, in the mes- and diencephalon, one of the tectofugal pathways and its target nuclei, here called the tecto-pretecto-rotundal system, express N-cadherin. R-cadherin is expressed by a different tectofugal system, the tectoisthmic pathway. The other tectofugal systems express neither N- nor R-cadherin. In addition, a small number of other mes- and diencephalic nuclei express N- or R-cadherin. On the basis of these results and experimental evidence from other studies, we speculate that the two cadherins are involved in the formation and segregation of particular functional systems within the vertebrate central nervous system (CNS) by regulating the formation of nuclei, and the pathfinding and/or the selective fasciculation of neurites. Apart from neuronal elements, a variety of vascular and ependymal structures also express N-cadherin or R-cadherin, e.g., the parenchymal blood vessels, the choroid plexus, the floor and roof plates, and the ventricular lining. These findings suggest that the two cadherins play a variety of roles during the development of neuronal and nonneuronal epithelial structures throughout CNS development.

Animals↗
PubMed1993

Expression of N-cadherin mRNA during development of the mouse brain.

The expression of N-cadherin mRNA was mapped in the brain of mice between embryonic day 12 (E12) and the adult stage by in situ hybridization of digoxigenin-labeled riboprobe. Two phases of N-cadherin expression can be distinguished. During the first phase (about E12 to E16), expression is ubiquitous throughout the brain and most prominent in the proliferative neuroepithelium. During the second phase (about E16 to postnatal day 6), N-cadherin expression is restricted to particular nuclei or laminae that share common functional features and neuroanatomical connections. Several of the N-cadherin-positive structures receive direct afferents from retinal ganglion cells or from the superior colliculus. Others belong to the reticular system and to the limbic system of the brain. In neocortex, N-cadherin is expressed by deeper layer cells. In the adult brain, only low levels of N-cadherin expression remain in very few types of cells, for example in the Purkinje cells of the cerebellum. These results are similar to data from chicken brain and suggest that the generalized expression of N-cadherin during the early phase and the restriction expression of this molecule in particular functional systems during the later phase is, at least in part, phylogenetically conserved between chicken and mouse. Moreover, the results show that N-cadherin expression extends to phylogenetically newer structures, e.g., the mammalian neocortex.

Animals↗
PubMed1993

N- and R-cadherin expression in the optic nerve of the chicken embryo.

Cadherins are a family of molecules mediating Ca(2+)-dependent cell-cell adhesion in various tissues. N- and R-cadherin are expressed in the chick embryonic CNS and differ in their expression pattern during development. Here we focus on the differential expression of N- and R-cadherin in the early optic nerve. N-cadherin is expressed by the retinal neurites growing through the optic nerve. R-cadherin is expressed by the early optic nerve glia, which derives from the optic stalk neuroepithelium and corresponds to an immature form of the type-1 astrocyte described in rat optic nerve. The close contact between the plasma membranes of the retinal neurites and the optic nerve glia is believed to be important in guiding retinal axons through the optic nerve. Using neuroblastoma cell lines transfected with R-cadherin, we demonstrate that the N-cadherin-positive retinal axons can use R-cadherin as a substrate for axon elongation. These results suggest that the R-cadherin expressed by the early optic nerve glia might provide a molecular substrate for the growth of N-cadherin-positive retinal axons through the optic nerve.

Animals↗
PubMed1992

Restricted expression of N- and R-cadherin on neurites of the developing chicken CNS.

The expression of two cadherins, N- and R-cadherin, was mapped in the CNS of chicken embryos of 6-11 d incubation, focusing on the sensory and motor fiber systems. In the spinal cord, the laterally located fibers of the dorsal funiculus express N-cadherin while the medially located fibers do not. These two fiber systems have a different course within the CNS but associate to form the spinal dorsal roots. In the hindbrain, N-cadherin is expressed by the descending trigeminal (general somatic sensory) tract, which is contiguous with the N-cadherin-positive zone of the dorsal funiculus of the spinal cord. R-cadherin is not expressed by sensory fibers, but is expressed by the visceral motor system of the vagus and glossopharyngeal nerves, which are N-cadherin negative. The motor neurites expressing R-cadherin have a different course within the brain than the sensory neurites expressing N-cadherin, although they form the common sensory/motor roots of the vagus nerve at the surface of the brain. The possibility that N-cadherin provides a guidance cue for sensory axon migration within the CNS by a homophilic adhesion mechanism was investigated in vitro. Explants from sensory spinal ganglia expressing N-cadherin were placed on N-cadherin-transfected neuroblastoma cells, and axon outgrowth was visualized. Results showed that the sensory axons defasciculate and closely follow the cell-cell boundaries between transfected cells where high levels of N-cadherin are expressed. These results show that the two cadherins, like members of the immunoglobulin superfamily of molecules, are expressed in a topographically restricted fashion during chick brain development. They furthermore suggest that N-cadherin expression by neurites may play a role in guiding these neurites along CNS paths that express the same molecule.

Animals↗
PubMed1991

Differentiation and heterogeneity in T-antigen immortalized precursor cell lines from mouse cerebellum.

Recently, various techniques have been developed to transfer oncogenes into brain cells in order to generate immortalized neural cell lines. It is of interest to establish how well such cell lines reflect their cellular origin. Here we report the characterization of sixteen cell lines from mouse cerebellum and, as a control, six cell lines from skin. Lines were established by immortalizing postnatal primary cell cultures with a retrovirus carrying a modified temperature-sensitive variant of SV40 large T antigen. The cell lines reflect many properties of the cell type from which they were derived. All of the sixteen cerebellar lines expressed one or more markers of the neural precursor cells, namely, nestin and epitopes for NG2 and A2B5. In contrast, none of the six skin lines expressed neural precursor markers. Both types of cell lines expressed vimentin and fibronectin. Differentiation occurred in some of the cerebellar lines and was enhanced in defined medium. A small percentage of cerebellar cells, usually less than 5%, was positive for a marker of differentiation, e.g., glial fibrillary acidic protein (GFAP), galactocerebroside (GalC), or L1. Expression of GFAP colocalized with that of nestin at varying levels of intensity, indicating a gradual replacement of nestin by GFAP in the cytoskeleton. Both the cells positive for precursor markers and those positive for differentiation markers tended to be located in clusters, suggesting that stochastic processes or cell-cell interactions are important for the determination of the fate of cells within a clonal cell line in vitro. The degree of differentiation seemed to correlate with a shift from serum-containing to defined medium, but not with a shift from the permissive to the nonpermissive temperature for T antigen expression. The immortalization approach described here thus allows the establishment of cell lines which are "captured" in the precursor state of the developing mouse neuroepithelium.

Animals↗
PubMed1991

Differential expression of R- and N-cadherin in neural and mesodermal tissues during early chicken development.

R-cadherin is a newly identified member of the cadherin family of cell adhesion receptors. The expression of R-cadherin in early chicken embryos was studied using affinity-purified antibodies to this molecule, comparing it with that of N-cadherin. Immunoblot analysis of various organs of 10.5-day embryos showed that R-cadherin is most abundantly expressed in the retina and brain. Immunostaining of the cervical and thoracic regions of embryos revealed that R- and N-cadherin are expressed in all neural tissues. In the neural tube, R-cadherin appears at around stage 21, although N-cadherin expression begins at a much earlier stage. The distribution of R-cadherin in the neural tube differs from that of N-cadherin; for example, some regions of the tube express only R-cadherin, and other regions only N-cadherin. In the peripheral ganglia, these two cadherins are also expressed in different patterns which change during development. Some mesenchymal tissues including the notochord, the myotome, myotubes and perichondria also express these cadherins, again in different patterns. Thus, R- and N-cadherin are differentially expressed in all the tissues examined, and they may contribute to the spatial segregation of heterogeneous cells in a tissue.

Animals↗
PubMed1990

Functional organization in the ferret visual cortex: a double-label 2-deoxyglucose study.

The functional organization of visual cortical area 17/18 of the ferret was studied using a double-label 2-deoxyglucose (2-DG) method. Animals were stimulated sequentially with moving gratings of 2 different orientations. Elongated orientational patches running roughly at a right angle into the area 17/18 border were seen. The orientation maps were similar in areas 17 and 18. When animals were stimulated with 2 orthogonally oriented gratings, activation patterns were not fully complementary but did not overlap. A complex pattern of partial overlap was observed, with orientations differing by 45 degrees. More gradual and more abrupt changes alternated frequently on a scale smaller than the average periodicity in the patterns. A cortical patch representing a given orientation was regularly surrounded by both neighboring and orthogonal orientations. The direction of the orientational changes reversed frequently in the immediate vicinity of any orientational patch. Orientation maps were compared with complete maps of retino-cortical projections obtained by transneuronal labeling with intravitreally injected tritiated proline. Ocular dominance in the binocular segment of both areas 17 and 18 was found to be organized into elongated ipsilateral islands in an almost contiguous contralateral projection. In area 18, the patches were wider than in area 17, and the ipsilateral islands were smaller in the regions representing the upper and central visual field than in those representing the lower visual field.

Animals↗
PubMed1989

Discontinuities along lines: psychophysics and neurophysiology.

If a segment of a line differs in luminance or color from the rest of the line, three illusory phenomena may be perceived: a reduction in contrast of the line segment relative to the background, subjective contours running perpendicularly to the ends of the line segment, and spread of color or brightness surrounding the line segment. All three phenomena cause a perceptual enhancement of the line discontinuity. Their psychophysical properties and possible neurophysiological correlates in the visual cortex are discussed. Contrast reduction has characteristics similar to end-stopped neuronal responses. Subjective contours elicit orientation-specific neuronal responses in areas 17 and 18. Neon color and brightness spreading may be mediated by "dot-responsive" cells in area 19.

Animals↗
PubMed1989

The deoxyglucose method in the ferret brain. I. Methodological considerations.

In the brain of the anesthetized ferret, the 2-deoxyglucose (2-DG) transfer rate constants required to determine cerebral glucose utilization by the deoxyglucose method were calculated from regional gray matter time-radioactivity curves measured for 180 min after tracer injection. Results suggest that loss of metabolized tracer from brain occurs at a rate of about 1%/min for the first 180 min after injection if the rate constant of the rate-limiting step for loss of metabolized tracer (k4*) represents a first-order kinetic process. A simulation experiment shows that, whether k4* is assumed to be 0 or 0.01 min-1, has a negligible influence on glucose utilization rates obtained in conventional 45 min autoradiographic experiments provided that the entire analysis, including lumped constant determination, is carried out in a consistent way. The 2-DG lumped constant for k4* = 0 is 0.54, and 0.68 for k4* = 0.01 min-1.

Animals↗
PubMed1989

The deoxyglucose method in the ferret brain. II. Glucose utilization images and normal values.

To measure cerebral glucose utilization with the autoradiographic deoxyglucose method, the tracer transfer rate constants and lumped constants must be known. 2-Deoxyglucose (2-DG) and fluorodeoxyglucose (FDG) constants were determined in 18 gray and white matter brain structures of the anesthetized ferret. The ferret is a domestic carnivore particularly suitable for deoxyglucose studies because of its small brain size and low body weight. The average gray matter rate constants for tracer transfer across the blood-brain barrier are similar for 2-DG and FDG in the ferret brain (K*1 = 0.21 ml/g/min and k*2 = 0.39 min-1). The rate constant for the rate-limiting step of tracer phosphorylation, k*3, is 1.6 times higher for FDG than for 2-DG (0.21 vs. 0.13 min-1). Loss of metabolized tracer is about 1-1.5%/min throughout the ferret brain for both tracers as estimated for a 180 min experimental period. Taking into account this loss, the lumped constant is 0.92 for FDG and 0.68 for 2-DG. Glucose utilization values in the brain of the anesthesized ferret range from 33 mumol/100 g/min in the corpus callosum to 104 mumol/100 g/min in the caudate nucleus. Representative glucose utilization images of coronal sections of the ferret brain are shown. Brain structures are identified on the same slices counterstained with thionin.

Animals↗
PubMed1989

Generalized decrease in brain glucose metabolism during fasting in humans studied by PET.

In prolonged fasting, the brain derives a large portion of its oxidative energy from the ketone bodies, beta-hydroxybutyrate and acetoacetate, thereby reducing whole body glucose consumption. Energy substrate utilization differs regionally in the brain of fasting rat, but comparable information has hitherto been unavailable in humans. We used positron emission tomography (PET) to study regional brain glucose and oxygen metabolism, blood flow, and blood volume in four obese subjects before and after a 3-wk total fast. Whole brain glucose utilization fell to 54% of control (postabsorptive) values (P less than 0.002). The whole brain rate constant for glucose tracer phosphorylation fell to 51% of control values (P less than 0.002). Both parameters decreased uniformly throughout the brain. The 2-fluoro-2-deoxy-D-glucose lumped constant decreased from a control value of 0.57 to 0.43 (P less than 0.01). Regional blood-brain barrier transfer coefficients for glucose tracer, regional oxygen utilization, blood flow, and blood volume were unchanged.

Adult↗
PubMed1989

Double-label and conventional deoxyglucose methods: a practical guide for the user.

The autoradiographic deoxyglucose method is widely used to map functional activity in mammalian brain. Whereas the method is simple to use, the underlying kinetic model is complex. This paper reviews the deoxyglucose kinetic model and the relevant implications for the user who does not have extensive knowledge of tracer kinetics. In generally understandable terms, single-label and double-label deoxyglucose approaches are discussed. Experimental procedures are described in detail. The calculations required for qualitative and quantitative experiments are explained. The deoxyglucose method is compared to other methods that map functional activity in mammalian brain.

Animals↗