A. Moscona, A. Wiens
May 1, 1975
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Developmental biology
Abstract
Abstract Proflavine (3,6-diaminoacridine) was shown to be an effective molecular probe for analysis of a tissue-specific gene expression in embryonic neural retina cells. The induction by hydrocortisone of glutamine synthetase (GS), a marker of differentiation in the developing retina, is differentially and reversibly blocked by proflavine. Concentrations of proflavine that totally inhibit the synthesis of enzymatically and immunologically reactive GS only minimally reduce total RNA and protein synthesis. Proflavine does not hinder the uptake of steroid inducer into retina cells and its binding to cytoplasmic receptors; nor does it directly prevent the translation of GS mRNA. The evidence suggests that proflavine hinders, reversibly and differentially, processes necessary for the provision of functional transcripts for GS synthesis. Replication of DNA is not required for the reversible inhibition by proflavine of GS synthesis; nor is suppression of DNA synthesis by proflavine causally involved in its effect on GS. Thus, proflavine functions in this case as a nonmutagenic, differential modifier of gene expression. Structural features of the proflavine molecule and related derivatives relevant to this effect have been determined. The results warrant further exploration of proflavine and related molecules as probes of specific gene expression in this and other systems.