Edgar B A, Lehman D A, O'Farrell P H
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Development. 1994 Nov;120(11):3131-43. doi: 10.1242/dev.120.11.3131.
During postblastoderm embryogenesis in Drosophila, cell cycles progress in an invariant spatiotemporal pattern. Most of these cycles are differentially timed by bursts of transcription of string (cdc25), a gene encoding a phosphatase that triggers mitosis by activating the Cdc2 kinase. An analysis of string expression in 36 pattern-formation mutants shows that known patterning genes act locally to influence string transcription. Embryonic expression of string gene fragments shows that the complete pattern of string transcription requires extensive cis-acting regulatory sequences (> 15.3 kb), but that smaller segments of this regulatory region can drive proper temporal expression in defined spatial 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 largely unaffected in mutant embryos specifically arrested in G2 of cycles 14, 15, or 16, or G1 of cycle 17. Thus, there is a regulatory hierarchy in which developmental inputs, not cell cycle inputs, control the timing of string transcription and hence cell cycle progression.
在果蝇胚盘后期胚胎发育过程中,细胞周期按照不变的时空模式进行。这些周期中的大多数通过“String”(cdc25)基因转录的爆发而有不同的时间安排,“String”是一种编码磷酸酶的基因,该磷酸酶通过激活Cdc2激酶来触发有丝分裂。对36个模式形成突变体中“String”表达的分析表明,已知的模式形成基因在局部发挥作用以影响“String”转录。“String”基因片段的胚胎表达表明,“String”转录的完整模式需要广泛的顺式作用调控序列(>15.3 kb),但该调控区域的较小片段可在特定空间域驱动适当的时间表达。我们推断,“String”上游序列整合了许多局部信号以指导“String”的转录程序。最后,我们表明,在特定停滞于第14、15或16周期的G2期或第17周期的G1期的突变胚胎中,“String”转录的时空进程基本不受影响。因此,存在一种调控层次结构,其中发育输入而非细胞周期输入控制“String”转录的时间,进而控制细胞周期进程。