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Biomedical subjects

D I Gottlieb

Publications and source records attributed to D I Gottlieb.

At least 55 records · Page 3Linked to original sources

A monoclonal antibody which binds to the surface of chick brain cells and myotubes: cell selectivity and properties of the antigen.

A monoclonal antibody has been obtained which binds to the cell surface of cultured chick myotubes and retinal and tectal neurons but not fibroblasts, myoblasts and embryonic liver cells. Indirect immunocytochemistry reveals that antigen is present in all layers of the chick neural retina. The antibody therefore recognizes an antigen common to most, if not all, chick neurons. The antigen has been identified by staining SDS gels with [125I]monoclonal antibody and appears to be a polydisperse collection of polypeptides with molecular weights centered about 250 kdalton.

Animals↗

Monoclonal antibodies selective for the inner portion of the chick retina.

Five monoclonal antibodies were selected by immunizing mice with embryonic chick optic nerve and screening the resultant hybridoma antibodies by immunofluorescence on sections of the retina. The optic nerve was chosen as the immunizing tissue since it is presumably enriched in ganglion cell-specific antigens. These antibodies bind to antigens which are largely localized to the inner part of the retina. Two of the antibodies, RET1 and RET2, show highly selective binding to the optic fiber layer. Another, RET3, stains the optic fiber layer, ganglion cell layer, and inner plexiform layer. Antibody RET4 stains the optic fiber layer, ganglion cell layer, inner plexiform layer, and the inner one-half of the inner nuclear layer; this antibody binds to an antigen on or associated with the plasma membrane. Antibody RET5 stains the retinal ganglion cell layer faintly and the inner and outer plexiform layers strongly. The potential utility of these antibodies for future studies on retinal development is discussed.

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Developmental changes in glycoproteins of the chick nervous system.

Temporal changes have been noted previously in retinal glycoproteins that bind to wheat germ agglutinin by a technique in which the denatured glycoproteins are first separated according to size by polyacrylamide gel electrophoresis, and are then localized on the gel using [125I]lectin. As reported here this technique will also detect differences between dorsal and ventral halves of the neural retina from 8-day chick embryos, and using other lectins will detect temporal changes in the glycoprotein pattern of the optic tectum. Some of the glycoproteins detected by wheat germ agglutinin in the neural retina appear to be represented on the surface of the retinal cells since: (a) the temporal changes in retinal glycoproteins can also be observed in a plasma membrane enriched fraction prepared from neural retina cells; and (b) antibodies prepared in mice against various size categories of wheat germ lectin binding glycoproteins bind to intact retinal cells.

Aging↗

Studies on cell recognition in the developing brain.

Several lines of evidence demonstrate cell-cell receptors on the surface of developing brain cells. Plasma membrane vesicles with regional and temporal binding specificities can be prepared. Active factors that block cell aggregation can be extracted from these membranes and partially purified. Quantitative studies of cell-cell adhesion demonstrate a gradient of adhesive specificity along the dorsoventral axis of the developing retina.

Animals↗

A gradient of adhesive specificity in developing avian retina.

Cell-cell adhesion was examined in the developing chick neural retina. A dorsoventral gradient of adhesive specificity in dissociated cells was detected which exhibits a complementarity such that the highest cell-cell affinities are exhibited between cells derived from the extremes of the gradient. If a nasotemporal gradient exists it must exhibit significantly lower cell-cell affinity. The relevance of these findings to pattern formation in the nervous system is discussed.

Age Factors↗

Embryonal cell surface recognition. Extraction of an active plasma membrane component.

Plasma membranes obtained from different neural regions of the chicken embryo have previously been shown to specifically bind to homotypic cells and prevent cell aggregation (Merrell, R., and Glaser, L. (1973) Proc. Natl. Acad. Sci. U. S. A. 70, 2794-2798). Proteins responsible for the specific inhibition of cell aggregation have been solubilized from the plasma membrane of neural retina and optic tectum by delipidation with acetone followed by extraction with lithium diiodosalicylate. The extracts show the same regional and temporal specificity as previously shown for plasma membrane recognition by the same cells (Gottlieb, D. I., Merrell, R., and Glaser, L. (1974) Proc. Natl. Acad. Sci. U. S. A. 71, 1800-1802). Two micrograms of the most purified protein fraction inhibits the aggregation of 2.5 times 10(-4) cells under standard assay conditions. This represents a 20-fold increase in specific activity compared to whole membranes.

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An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat.

The dentate gyrus of the rat contains about 600,000 granule cells. These small neurons are generated over a prolonged period from the 14th day of gestation until some time after the second postnatal week. The majority of the cells pass through their last phase of DNA synthesis in the postnatal period, and during the peak period of cell generation, between the fifth and seventh days after birth, up to 50,000 granule cells are formed each day. Contrary to earlier reports, most of the cells pass through their last mitotic division either within the stratum granulosum itself, or within the hilar region of the developing gyrus. The precursor population of cells in the hilar region must therefore constitute a pool of true neuroblasts. The origin of this pool of cells has not been definitely established but it seems probable that its cells are derived from the neuroepithelium lining the lateral ventricle adjacent to the region from which the hippocampal pyramidal cells are generated. Examination of the final location of granule cells labeled at different stages reveals three distinct morphogenetic gradients in the gyrus. The cells in the dorsal blade tend to be formed earlier than those in the ventral blade; cells in the more caudal (or temporal) portions of the gyrus are generated earlier than those in more rostral (or septal) regions; and in all regions the more superficial neurons in the stratum granulosum are formed earlier than the deeper granule cells. The bearing of some of these findings on the development and organization of the connections of the dentate gyrus is discussed.

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Temporal changes in embryonal cell surface recognition.

Plasma membranes have been prepared from optic tectum and neural retina of chick embryos. These membranes specifically inhibit the aggregation of homotypic cells. Plasma membranes prepared from each of these regions obtained from chick embryos at 7,8, and 9 days of development show specificity for homotypic cells of the same age and cross-react weakly with homotypic cells of different ages. Thus cell-surface recognition changes with age of development, and most of the cells in each region have a common cell-surface recognition specificity. Tectal cells react weakly with retinal cell membranes, but no inhibition of retinal cell aggregation by tectal cells has been noted.

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