TRANSCRIPTIONAL REGULATION OF STRING (CDC25) - A LINK BETWEEN DEVELOPMENTAL PROGRAMMING AND THE CELL-CYCLE

During postblastoderm embryogenesis in Drosophila, cell cycles progres s in an invariant spatiotemporal pattern. Most of these cycles are dif ferentially timed by bursts of transcription of string (cdc25), a gene encoding a phosphatase that triggers mitosis by activating the Cdc2 k inase. An analysis of string expression in 36 pattern-formation mutant s shows that known patterning genes act locally to influence string tr anscription. Embryonic expression of string gene fragments shows that the complete pattern of string transcription requires extensive cis-ac ting regulatory sequences (>15.3 kb), but that smaller segments of thi s regulatory region can drive proper temporal expression in defined sp atial domains. We infer that string upstream sequences integrate many local signals to direct string's transcriptional program. Finally, we show that the spatiotemporal progression of string transcription is la rgely unaffected in mutant embryos specifically arrested in Gz of cycl es 14, 15, or 16, or G(1) of cycle 17. Thus, there is a regulatory hie rarchy in which developmental inputs, not cell cycle inputs, control t he timing of string transcription and hence cell cycle progression.