THE DORSAL MORPHOGEN GRADIENT REGULATES THE MESODERM DETERMINANT TWIST IN EARLY DROSOPHILA EMBRYOS
THE DORSAL MORPHOGEN GRADIENT REGULATES THE MESODERM DETERMINANT TWIST IN EARLY DROSOPHILA EMBRYOS
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DOI：
10.1101/gad.5.10.1881
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发表时间：
1991-10-01
影响因子：
10.5
通讯作者：
LEVINE, M
中科院分区：
文献类型：
--
作者：
JIANG, J;KOSMAN, D;LEVINE, M
母体形态原dorsal（dl）的梯度启动了早期果蝇胚胎沿背腹轴沿着的各种组织的分化。dl是与哺乳动物调节因子NF-κ-B相关的序列特异性DNA结合蛋白。 先前的研究表明dl可以作为转录抑制因子发挥作用。 为了确定dl如何作为激活剂发挥作用，我们检测了中胚层决定因子基因twist（twi）的启动子。 遗传学研究表明，早期胚胎腹侧区域dl蛋白的峰值水平启动twi表达。 使用组合的启动子融合-P-转化试验，并在体外DNA结合试验加上定点诱变，我们建立了一个直接的联系DL-结合位点和twi在早期胚胎中的表达。 我们还提出的证据表明，背腹侧的限制twi的表达依赖于其启动子中存在的DL结合位点的数量和亲和力。 twi与第二个dl靶基因zen的比较表明dl结合位点的亲和力与对dl形态原不同阈值的反应之间存在相关性。
A gradient of the maternal morphogen dorsal (dl) initiates the differentiation of various tissues along the dorsal-ventral axis of early Drosophila embryos. dl is a sequence-specific DNA-binding protein that is related to the mammalian regulatory factor NF-kappa-B. Previous studies suggest that dl can function as a transcriptional repressor. To determine how dl functions as an activator we have examined the promoter of the mesoderm determinant gene twist (twi). Genetic studies suggest that peak levels of dl protein in ventral regions of early embryos initiate twi expression. Using a combination of promoter fusion-P-transformation assays, and in vitro DNA-binding assays coupled with site-directed mutagenesis, we establish a direct link between dl-binding sites and twi expression in the early embryo. We also present evidence that the dorsal-ventral limits of twi expression depend on the number and affinity of dl-binding sites present in its promoter. A comparison of twi with a second dl target gene, zen, suggests a correlation between the affinities of dl-binding sites and response to different thresholds of dl morphogen.