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A A Moscona

Publications and source records attributed to A A Moscona.

At least 91 records · Page 5Linked to original sources

Cell-surface interactions: differential inhibition by proflavine of embryonic cell aggregation and production of specific cell-aggregating factor.

Cell recognition and morphogenetic aggregation of embryonic cells into tissues are mediated by specific macromolecules in the cell surface (cell-aggregating factors). A factor specific for embryonic neural retina cells was demonstrated; its synthesis is required for histotypic reaggregation of retina cell suspensions. We show that proflavine (3,6-diaminoacridine) preferentially and reversibly suppresses production of the cell-aggregating factor and thereby inhibits normal cell reaggregation. If such proflavine-treated retina cells are exogenously supplied with the retina-specific factor, they reaggregate. The selectivity of these effects supports the postulated significance of specific cell-surface components in cell association into tissues; the results indicate that proflavine may be a useful molecular probe for studying formation of specific cell-surface components and their role in various cell interactions.

Acridines↗

Glutamine synthetase induction in embryonic neural retina: immunochemical identification of polysomes involved in enzyme synthesis.

Glutamine synthetase (EC 6.3.1.2) in embryonic neural retina in culture is rapidly induced by hydrocortisone. Retina polysomes involved in translation of this enzyme were precipitated with a high degree of specificity by the gammaglobulin isolated from antiserum against the enzyme (anti-enzyme gammaglobulin). Using immunoprecipitation procedures, we determined that the amount of polysome-bound nascent enzyme was maximal in polysomes comprising 9-14 ribosomes and was about 3-fold higher in the induced than in the noninduced retina. Within this size group of polysomes, those comprising 11-13 ribosomes showed consistently greater binding of anti-enzyme [(125)I]gammaglobulin than of normal [(125)I]-gammaglobulin. This size of polysomes corresponds to that calculated for a monocistronic messenger RNA for the subunit of this enzyme, which has a molecular weight of 42,000. The application of immunochemical techniques to identification of templates for synthesis of an enzyme in embryonic cells that constitutes less than 1% of the total cellular proteins indicates the usefulness of this method for detailed studies on regulation of other quantitatively minor products significant in cell differentiation.

Amino Acids↗

Preferential inhibition by proflavine of the hormonal induction of glutamine synthetase in embryonic neural retina.

The hormonal induction of glutamine synthetase (EC 6.3.1.2) in embryonic neural retina tissue in vitro is blocked preferentially and reversibly by proflavine (3,6-diaminoacridine) in the absence of cell or DNA replication; cell viability is not affected, and the synthesis of total cellular proteins and RNA is only slightly reduced. In the induction of this enzyme, there is a rapid increase in the synthesis and accumulation of the enzyme selectively elicited by the steroid inducer; for this effect, transcription is essential. Radioimmunochemical measurements have shown that proflavine inhibits induction by prevention of de novo synthesis of catalytically active and immunologically reactive glutamine synthetase protein. It does not measurably affect the uptake of the steroid inducer by the retina cells. Since the translation of this enzyme by preformed RNA templates is not stopped by proflavine, the inhibitory effect of proflavine on induction is apparently due to interference with transcriptional or pretranslational processes required for the provision of active transcripts for enzyme synthesis. The finding that proflavine inhibits preferentially a tissue-specific, inducible differentiation in postmitotic embryonic neural cells offers new approaches to the study of regulation of gene expression in eukaryotes.

Acridines↗

Tissue-specific cell-surface antigens in embryonic cells.

With the use of antisera prepared in rabbits against suspensions of live embryonic chick tissue cells, qualitative differences in cell surface antigens were demonstrated on cells from different embryonic chick tissues by immune agglutination and immunofluorescence. Unabsorbed antisera reacted with both homologous and nonhomologous cells; thorough absorption of the antisera with heterologous tissues removed cross-reacting antibodies, and the antisera acquired a high degree of tissue specificity. Thus, antiretina cell serum absorbed with nonretina cells or tissues, agglutinated only neural retina cells, and was shown by immunofluorescence tests to react specifically with the surface of retina cells, both in cell suspensions and in frozen tissue sections. Comparable results with antisera against cells from embryonic liver and other tissues demonstrated the existence of tissue-specific, phenotypic disparities in the antigenicities of embryonic cell surfaces, in addition to the presence of cell-surface antigens shared by certain classes of cells, and of antigens common to all cells in the embryo. The results are discussed in terms of the possible involvement of such phenotypic determinants in the specification of cell surfaces, in relation to cell recognition and developmental interactions.

Agglutination Tests↗

Embryonic and neoplastic cell surfaces: availability of receptors for concanavalin A and wheat germ agglutinin.

Embryonic tissue cells dissociated with ethylenediaminetetraacetate are readily agglutinated by the carbohydrate-binding protein concanavalin A. In this property, they resemble transformed, neoplastic cells; and they differ from untransformed adult cells, which are agglutinated by concanavalin A only after their receptors are unmasked by proteolytic treatment. Receptor sites for wheat germ agglutinin are also present on the surface of embryonic cells, but in a masked form, as on untransformed adult culture cells; they can be unmasked by treatment of the cells with trypsin. Concanavalin A binding sites on embryonic cells may function in cell contact and cell organization during embryonic morphogenesis and differentiation and later become masked in adult cells. The unmasking of these sites in neoplastic cells may represent a return, in this respect, to a condition resembling that of embryonic cells and may be related to cell mobility associated with infiltration and metastasis.

Agglutination↗

Changes in macromolecular synthesis associated with the induction of glutamine synthetase in embryonic retina.

The hydrocortisone-mediated induction of glutamine synthetase in the neural retina of chicken embryo in vitro is correlated with enhanced incorporation into protein of [(14)C]aspartic acid, an amino acid abundant in this enzyme. In the induced retina labeled with [(14)C]aspartic acid, a peak of radioactivity was detected in the region of the polysomal profile corresponding to polysomes comprising 12-14 ribosomes. In retinas labeled with [(3)H]uridine, an increased amount of radioactivity was also detected in the same polysomal region of the hydrocortisone-induced retina. If we assume a monocistronic messenger RNA for retinal glutamine synthetase, this region corresponds to the estimated size of the polysomes necessary for the translation of this enzyme. The evidence presented demonstrates a correlation between these changes in incorporation and the induction of glutamine synthetase.

Animals↗

Induction of glutamine synthetase in embryonic retina: its dependence on cell interactions.

A relation between enzyme induction in embryonic cells and cellular organization is indicated by the finding that the levels of glutamine synthetase induced by hydrocortisone in the embryonic neural retina in vitro are dependent on the associations between the retina cells. Intact retina tissue, aggregates of dissociated cells, and cells in monolayer culture showed a decreasing response, in this order, to glutamine synthetase induction. With time of culture, the enzyme activity continued to rise in the intact retina and in cell aggregates, but activity declined in monolayer cultures even though the inducer was continuously present. Dispersed cells cultured in monolayer without the inducer showed after 24 hours a loss of inducibility which could not be reversed by reaggregating such modified cells but could be prevented by maintaining the freshly dispersed cells at a low temperature.

Animals↗