Edgar B A, Odell G M, Schubiger G
Department of Biochemistry and Biophysics, University of California, San Francisco.
Dev Genet. 1989;10(3):124-42. doi: 10.1002/dvg.1020100303.
The pair-rule genes hairy, runt, even-skipped, and fushi tarazu express their mRNAs and proteins in striped patterns in the Drosophila embryo at the blastoderm stage. Previous studies have shown that the generation of these patterns depends upon products of the gap genes and upon interactions between the pair-rule genes themselves. Here we show that blocking protein synthesis induces expression of each of the pair-rule mRNAs in virtually all regions of the embryo. Our observations together with genetic studies carried out in other laboratories suggest that negative feedback between the pair-rule genes plays a key role in striped expression of pair-rule genes. We propose that stable proteins, present in all regions of the embryo, first activate transcription of these pair-rule genes constitutively. Then, various combinations of unstable proteins repress their transcription in a patterned fashion; each stripe of accumulated products of a given pair-rule gene marks a region where it was not repressed. We develop this idea in mathematical form and demonstrate that a network of mutual repression by pair-rule genes can make each blastoderm nucleus into a genetic switch with two stable states. If preexisting gap gene patterns provide initial bias to the blastoderm nuclei, then the "bistable switch behavior" of the nuclei can refine an initially weak spatial bias into a final pattern of sharp stripes.
成对规则基因hairy、runt、even-skipped和fushi tarazu在果蝇胚胎囊胚期以条纹模式表达其mRNA和蛋白质。先前的研究表明，这些模式的产生依赖于缺口基因的产物以及成对规则基因自身之间的相互作用。在此我们表明，阻断蛋白质合成会在胚胎的几乎所有区域诱导每个成对规则mRNA的表达。我们的观察结果以及其他实验室进行的遗传学研究表明，成对规则基因之间的负反馈在成对规则基因的条纹表达中起关键作用。我们提出，存在于胚胎所有区域的稳定蛋白质首先组成性地激活这些成对规则基因的转录。然后，不稳定蛋白质的各种组合以模式化方式抑制它们的转录；给定成对规则基因积累产物的每条条纹标记了其未被抑制的区域。我们以数学形式阐述了这一观点，并证明成对规则基因相互抑制的网络可使每个囊胚细胞核成为具有两种稳定状态的遗传开关。如果预先存在的缺口基因模式为囊胚细胞核提供初始偏差，那么细胞核的“双稳态开关行为”可将最初微弱的空间偏差细化为最终清晰的条纹模式。
