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  • 1985-1989  (7)
  • 1
    Online Resource
    Online Resource
    Rockefeller University Press ; 1986
    In:  The Journal of cell biology Vol. 103, No. 1 ( 1986-07-01), p. 145-158
    In: The Journal of cell biology, Rockefeller University Press, Vol. 103, No. 1 ( 1986-07-01), p. 145-158
    Abstract: Individual neurons can express both the neural cell adhesion molecule (N-CAM) and the neuron-glia cell adhesion molecule (Ng-CAM) at their cell surfaces. To determine how the functions of the two molecules may be differentially controlled, we have used specific antibodies to each cell adhesion molecule (CAM) to perturb its function, first in brain membrane vesicle aggregation and then in tissue culture assays testing the fasciculation of neurite outgrowths from cultured dorsal root ganglia, the migration of granule cells in cerebellar explants, and the formation of histological layers in the developing retina. Our strategy was initially to delineate further the binding mechanisms for each CAM. Antibodies to Ng-CAM and N-CAM each inhibited brain membrane vesicle aggregation but the binding mechanisms of the two CAMs differed. As expected from the known homophilic binding mechanism of N-CAM, anti-N-CAM-coated vesicles did not co-aggregate with uncoated vesicles. Anti-Ng-CAM-coated vesicles readily co-aggregated with uncoated vesicles in accord with a postulated heterophilic binding mechanism. It was also shown that N-CAM was not a ligand for Ng-CAM. In contrast to assays with brain membrane vesicles, cellular systems can reveal functional differences for each CAM reflecting its relative amount (prevalence modulation) and location (polarity modulation). Consistent with this, each of the three cellular processes examined in vitro was preferentially inhibited only by anti-N-CAM or by anti-Ng-CAM antibodies. Both neurite fasciculation and the migration of cerebellar granule cells were preferentially inhibited by anti-Ng-CAM antibodies. Anti-N-CAM antibodies inhibited the formation of histological layers in the retina. The data on perturbation by antibodies were correlated with the relative levels of expression of Ng-CAM and N-CAM in each of these different neural regions. Quantitative immunoblotting experiments indicated that the relative Ng-CAM/N-CAM ratios in comparable extracts of brain, dorsal root ganglia, and retina were respectively 0.32, 0.81, and 0.04. During culture of dorsal root ganglia in the presence of nerve growth factor, the Ng-CAM/N-CAM ratio rose to 4.95 in neurite outgrowths and 1.99 in the ganglion proper, reflecting both polarity and prevalence modulation. These results suggest that the relative ability of anti-Ng-CAM and anti-N-CAM antibodies to inhibit cell-cell interactions in different neural tissues is strongly correlated with the local Ng-CAM/N-CAM ratio.(ABSTRACT TRUNCATED AT 400 WORDS)
    Type of Medium: Online Resource
    ISSN: 0021-9525 , 1540-8140
    RVK:
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 1986
    detail.hit.zdb_id: 1421310-2
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1985
    In:  Proceedings of the National Academy of Sciences Vol. 82, No. 20 ( 1985-10), p. 6942-6946
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 82, No. 20 ( 1985-10), p. 6942-6946
    Abstract: A reexamination of the expression of cell adhesion molecules (CAMs) during the development of the chicken embryo was carried out using more sensitive immunocytochemical techniques than had been used previously. While the previously determined sequence of CAM expression was confirmed, neural CAM (N-CAM) was also detected on endodermal structures such as the lung epithelium, gut epithelium, and pancreas and on budding structures such as the pancreatic duct and gall bladder. It was also found on ectodermal derivatives of the skin. In most of these sites, N-CAM expression was transient, but in the chicken embryo lung, the epithelium remained positive for N-CAM and liver CAM (L-CAM) into adult life. Thus, at one time or another, both of these primary CAMs can be expressed on derivatives of all three germ layers. At sites of embryonic induction, epithelial cells expressing both L-CAM and N-CAM, or L-CAM only, were apposed to mesenchymal cells expressing N-CAM. Examples included epiblast (NL) and notochord (N); endodermal epithelium (NL) and lung mesenchyme (N); Wolffian duct (NL) and mesonephric mesenchyme (N); apical ectodermal ridge (NL) and limb mesenchyme (N); and feather placode (L) and dermal condensation (N). The cumulative observations indicate that cell surface modulation of the primary CAMs at induction sites can be classified into two modes. In mode I, expression of N-CAM (or both CAMs) in mesenchyme decreases to low amounts at the cell surface, and then N-CAM is reexpressed. In mode II, one or the other CAM disappears from epithelia expressing both CAMs. As a result of the primary processes of development, collectives of cells linked by N-CAM and undergoing modulation mode I are brought into the proximity of collectives of cells linked by L-CAM plus N-CAM or by L-CAM undergoing modulation mode II. Such adjoining cell collectives or CAM couples were found at all sites of embryonic induction examined.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1985
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Rockefeller University Press ; 1987
    In:  The Journal of cell biology Vol. 104, No. 2 ( 1987-02-01), p. 331-342
    In: The Journal of cell biology, Rockefeller University Press, Vol. 104, No. 2 ( 1987-02-01), p. 331-342
    Abstract: We have correlated the times of appearance of the neural cell adhesion molecule (N-CAM), the neuron-glia cell adhesion molecule (Ng-CAM), and the extracellular matrix protein, cytotactin, during the development of the chicken cerebellar cortex, and have shown that these molecules make different functional contributions to granule cell migration. Immunofluorescent staining showed distinct spatiotemporal expression sequences for each adhesion molecule. N-CAM was present at all times in all layers. However, the large cytoplasmic domain polypeptide of N-CAM was always absent from the external granular layer and was enriched in the molecular layer as development proceeded. Ng-CAM began to be expressed in the premigratory granule cells just before migration and later disappeared from cell bodies but remained on parallel fibers. Cytotactin, which is synthesized by glia and not by neurons, appeared first in a speckled pattern within the external granular layer and later appeared in a continuous pattern along the Bergmann glia; it was also enriched in the molecular layer. After we established their order of appearance, we tested the separate functions of these adhesion molecules in granule cell migration by adding specific antibodies against each molecule to cerebellar explant cultures that had been labeled with tritiated thymidine and then measuring the differential distribution of labeled cells in the forming layers. Anti-N-CAM showed marginal effects. In contrast, anti-Ng-CAM arrested most cells in the external granular layer, while anti-cytotactin arrested most cells in the molecular layer. Time course analyses combined with sequential addition of different antibodies in different orders showed that anti-Ng-CAM had a major effect in the early period (first 36 h in culture) and a lesser effect in the second part of the culture period, while anti-cytotactin had essentially no effect at the earlier time but had major effects at a later period (18-72 h in culture). The two major stages of cerebellar granule cell migration thus appear to be differentially affected by distinct adhesion molecules of different cellular origins, binding mechanisms, and overall distributions. The results indicated that local cell surface modulation of adhesion molecules of different specificities at defined stages and sites is essential to the formation of cerebellar cortical layers.
    Type of Medium: Online Resource
    ISSN: 0021-9525 , 1540-8140
    RVK:
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 1987
    detail.hit.zdb_id: 1421310-2
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Rockefeller University Press ; 1985
    In:  The Journal of cell biology Vol. 101, No. 3 ( 1985-09-01), p. 1027-1043
    In: The Journal of cell biology, Rockefeller University Press, Vol. 101, No. 3 ( 1985-09-01), p. 1027-1043
    Abstract: The developmental appearance of cell-adhesion molecules (CAMs) was mapped during the morphogenesis of the adult chicken feather. Neural CAM (N-CAM), liver CAM (L-CAM), and neuron-glia CAM (Ng-CAM), as well as substrate molecules (laminin and fibronectin), were compared in newborn chicken skin by immunohistochemical means. N-CAM was found to be enriched in the dermal papilla, which was closely apposed to L-CAM-positive papillar ectoderm. The two CAMs were then co-expressed in cells of the collar epithelium. Subsequently generated barb epithelia expressed only L-CAM, but N-CAM reappeared periodically on cells between developing barbs and barbules. N-CAM first appeared on a single L-CAM-positive basilar cell located in each valley flanked by two adjacent barb ridges. Subsequently, the expression of N-CAM extended one cell after another to include the whole basilar layer. N-CAM also appeared in the L-CAM-positive axial-plate epithelia, beginning in a single cell located at the ridge base. The two collectives of N-CAM-positive epithelia constituting the marginal and axial plates then disintegrated, leaving interdigitating spaces between keratinized structures that had previously expressed L-CAM. The morphological transformation from an epithelial cylinder to a three-level branched feather pattern is thus achieved by coupling alternating CAM expression in linked cell collectives with specific differentiation events, such as keratinization. During all of these morphogenetic processes, laminin and fibronectin formed a continuous basement membrane separating pulp from feather epithelia, and were excluded from the sites involved in periodic appearances of N-CAM. The same staining pattern described for developing chickens persisted in the feather follicles of adult chicken tissue that have gone through several cycles of molting. Cyclic expression of the two different CAMs underlies each of the different morphological events that are generated epigenetically during feather morphogenesis.
    Type of Medium: Online Resource
    ISSN: 0021-9525 , 1540-8140
    RVK:
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 1985
    detail.hit.zdb_id: 1421310-2
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1986
    In:  Proceedings of the National Academy of Sciences Vol. 83, No. 21 ( 1986-11), p. 8235-8239
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 83, No. 21 ( 1986-11), p. 8235-8239
    Abstract: Cell adhesion molecules (CAMs) may act as regulators of morphogenesis by constraining cell motion, forming borders, and controlling intercellular communications that lead to embryonic induction. This postulated causal role of CAMs in inductive events was tested here in an in vitro system of feather induction. In the developing chicken skin, an ectodermal sheet of epithelium interacts with mesodermal cell collectives to form more or less circular feather germs arranged in a hexagonal pattern. Cells of the epidermal epithelium are linked by liver CAM (L-CAM) and mesodermal cells in dermal condensations are linked by neural CAM (N-CAM); neither of these CAMs links cells in one tissue of this inductive couple to cells in the other. After perturbation of the L-CAM linkage in epidermis by antibodies to L-CAM, nonhexagonal striped patterns of dermal condensations were observed in culture. The stripes did not follow straight lines but meandered in lateral and oblique directions. Histological examination of the perturbed tissues showed extensive changes in dermal cell density distributions. After 10 days of culture, the perturbed tissues developed a cobbled or plaque-like morphology resembling scales rather than the feather-like filamentous structures that formed in unperturbed skin cultures. The results indicate that perturbation of CAM binding in tissues linked by one CAM can alter fates and interactions of cells linked by another, presumably by altering the amount or effect of inductive signals crossing the border between the inducing cell collectives. A computer model based on the notion that the response of L-CAM-linked epidermal cells to signals from N-CAM-linked dermal cells depends cooperatively on the degree of L-CAM linkage was found to generate hexagonal patterns for the unperturbed case and stripes after perturbation of L-CAM bonds.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1986
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Rockefeller University Press ; 1985
    In:  The Journal of cell biology Vol. 101, No. 3 ( 1985-09-01), p. 1009-1026
    In: The Journal of cell biology, Rockefeller University Press, Vol. 101, No. 3 ( 1985-09-01), p. 1009-1026
    Abstract: The potential relationship of cell adhesion to embryonic induction during feather formation was examined by immunohistochemical analysis of the spatiotemporal distribution of three cell-adhesion molecules (CAMs), neural CAM (N-CAM), liver CAM (L-CAM), and neuron-glia CAM (Ng-CAM), and of substrate molecules (laminin and fibronectin) in embryonic chicken skin. The N-CAM found at sites of embryonic induction in the feather was found to be similar to brain N-CAM as judged by immuno-cross-reactivity, migratory position in PAGE, and the presence of embryonic to adult conversion. In contrast to the N-CAM found in the brain, however, only one polypeptide of Mr 140,000 was seen. N-CAM-positive dermal condensations were distributed periodically under L-CAM-positive feather placodes at those sites where basement membranes are known to be disrupted. After initiation of induction, L-CAM-positive placode cells became transiently N-CAM-positive. N-CAM was asymmetrically concentrated in the dorsal region of the feather bud, while fibronectin was concentrated in the ventral region. During feather follicle formation, N-CAM was expressed in the dermal papilla and was closely apposed to the L-CAM-positive papillar ectoderm, while the dermal papilla showed no evidence of laminin or fibronectin. The collar epithelium was both N-CAM- and L-CAM-positive. During the formation of the feather filament, N-CAM appeared periodically and asymmetrically on basilar cells located in the valleys between adjacent barb ridges. In contrast to the two primary CAMs, Ng-CAM was found only on nerves supplying the feather and the skin. These studies indicate that at each site of induction during feather morphogenesis, a general pattern is repeated in which an epithelial structure linked by L-CAM is confronted with periodically propagating condensations of cells linked by N-CAM.
    Type of Medium: Online Resource
    ISSN: 0021-9525 , 1540-8140
    RVK:
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 1985
    detail.hit.zdb_id: 1421310-2
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Wiley ; 1988
    In:  International Journal of Clinical Practice Vol. 42, No. 6 ( 1988-06), p. 238-240
    In: International Journal of Clinical Practice, Wiley, Vol. 42, No. 6 ( 1988-06), p. 238-240
    Type of Medium: Online Resource
    ISSN: 1368-5031 , 1742-1241
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 1988
    detail.hit.zdb_id: 2135320-7
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