Expression of v-src in embryonic neural retina alters cell adhesion, inhibits histogenesis, and prevents induction of glutamine synthetase.
Using Rous sarcoma virus as the vector, v-src or c-src genes were introduced into 6-day chicken embryo retina tissue in organ culture and their effects on retina development were investigated. Overexpression of c-src in many of the cells had no noticeable effect on retina development. In contrast, infection with v-src resulted in abnormal histogenesis and inhibition of differentiation. Although only a portion of the cells in infected tissue expressed the oncogene and displayed the transformation phenotype, the other cells were also hindered from becoming normally positioned and organized. Therefore, presence of oncogene-transformed cells within the tissue hindered organization and development of adjacent nontransformed cells. Failure of normal cell relationships impeded induction by cortisol of glutamine synthetase in Muller glia, which requires contact associations of the glia cells with neurons. The transformed cells tended to assemble into chaotic clusters, suggesting that their adhesiveness and contact affinities had become altered. This was confirmed by aggregation experiments with dissociated cells which showed that adhesiveness of transformed cells was greatly reduced and that they had lost the ability to cohere with nontransformed cells. In binary mixtures of transformed and nontransformed cells, the two sorted out into separate aggregates. Transformed cells formed loose clusters devoid of tissue architecture; aggregates of nontransformed cells became organized into retinotypic structures, and glutamine synthetase was inducible. Our findings suggest that the mechanisms of cell adhesion and cell affinities are a key target of v-src activity in infected cells and that modification of the cell surface may be a leading factor in other cellular changes characteristic of the v-src transformation phenotype.
Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
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Vardimon
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Fox
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Cohen-Kupiec
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Degenstein
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Moscona
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D004790:Enzyme Induction; D015870:Gene Expression; D016391:Genes, src; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis* / Q000235:genetics; D009924:Organ Culture Techniques; D011233:Precipitin Tests; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000201:enzymology / Q000382:microbiology
D005974:Glutamate-Ammonia Ligase