Ip Y T, Park R E, Kosman D, Yazdanbakhsh K, Levine M
Biology Department, University of California, San Diego, La Jolla 92093-0322.
Genes Dev. 1992 Aug;6(8):1518-30. doi: 10.1101/gad.6.8.1518.
The first step in the differentiation of the Drosophila mesoderm is the activation of two regulatory genes, twist (twi) and snail (sna), in ventral regions of early embryos. sna is a transcriptional repressor that is uniformly expressed throughout the presumptive mesoderm. Its sharp lateral limits help to establish the boundary between the mesoderm and neuroectoderm. Genetic studies suggest that sna is a target of the dorsal (dl) morphogen, and this interaction provides a model for determining how a morphogen gradient establishes a sharp, on/off threshold response. We present evidence that dl and twi directly activate sna expression. Site-directed mutagenesis of dl- and twi-binding sites within defined regions of the sna promoter suggest that the two proteins (containing the Rel and helix-loop-helix domains, respectively) function multiplicatively to ensure strong, uniform expression of sna, particularly in ventral-lateral regions where there are diminishing amounts of dl. These results are consistent with the possibility that the sharp sna borders are formed by multiplying the shallow dl gradient and the steeper twi gradient.
果蝇中胚层分化的第一步是在早期胚胎的腹侧区域激活两个调控基因，即扭转基因（twi）和蜗牛基因（sna）。sna是一种转录抑制因子，在整个预定中胚层中均匀表达。其清晰的侧向边界有助于确立中胚层与神经外胚层之间的界限。遗传学研究表明，sna是背侧（dl）形态发生素的一个靶标，这种相互作用为确定形态发生素梯度如何建立清晰的开/关阈值反应提供了一个模型。我们提供的证据表明，dl和twi直接激活sna的表达。对sna启动子特定区域内的dl和twi结合位点进行定点诱变表明，这两种蛋白质（分别含有Rel结构域和螺旋-环-螺旋结构域）以相乘的方式发挥作用，以确保sna的强而均匀的表达，尤其是在dl含量逐渐减少的腹侧区域。这些结果与以下可能性一致，即清晰的sna边界是通过将浅的dl梯度和较陡的twi梯度相乘而形成的。
