Stein D, Goltz J S, Jurcsak J, Stevens L
Department of Molecular Genetics and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Development. 1998 Jun;125(11):2159-69. doi: 10.1242/dev.125.11.2159.
In Drosophila embryos, dorsal-ventral polarity is defined by a signal transduction pathway that regulates nuclear import of the Dorsal protein. Dorsal protein's ability to act as a transcriptional activator of some zygotic genes and a repressor of others defines structure along the dorsal-ventral axis. Dorsal is a member of a group of proteins, the Rel-homologous proteins, whose activity is regulated at the level of nuclear localization. Dif, a more recently identified Drosophila Rel-homologue, has been proposed to act as a mediator of the immune response in Drosophila. In an effort to understand the function and regulation of Rel-homologous proteins in Drosophila, we have expressed Dif protein in Drosophila embryos derived from dorsal mutant mothers. We found that the Dif protein was capable of restoring embryonic dorsal-ventral pattern elements and was able to define polarity correctly with respect to the orientation of the egg shell. This, together with the observation that the ability of Dif to restore a dorsal-ventral axis depended on the signal transduction pathway that normally regulates Dorsal, suggests that Dif protein formed a nuclear concentration gradient similar to that seen for Dorsal. By studying the expression of Dorsal target genes we found that Dif could activate the zygotic genes that Dorsal activates and repress the genes repressed by Dorsal. Differences in the expression of these target genes, as well as the results from interaction studies carried out in yeast, suggest that Dif is not capable of synergizing with the basic helix-loop-helix transcription factors with which Dorsal normally interacts, and thereby lacks an important component of Dorsal-mediated pattern formation.
在果蝇胚胎中，背腹极性由一条调节背蛋白核输入的信号转导通路决定。背蛋白作为一些合子基因的转录激活因子和另一些基因的抑制因子的能力决定了沿背腹轴的结构。背蛋白是一组蛋白（Rel同源蛋白）的成员，其活性在核定位水平受到调控。Dif是最近鉴定出的果蝇Rel同源物，有人提出它在果蝇中作为免疫反应的介质发挥作用。为了了解果蝇中Rel同源蛋白的功能和调控，我们在源自背突变体母亲的果蝇胚胎中表达了Dif蛋白。我们发现Dif蛋白能够恢复胚胎的背腹模式元件，并且能够相对于卵壳的方向正确地确定极性。这一点，连同观察到Dif恢复背腹轴的能力取决于正常调节背蛋白的信号转导通路，表明Dif蛋白形成了与背蛋白类似的核浓度梯度。通过研究背蛋白靶基因的表达，我们发现Dif可以激活背蛋白激活的合子基因，并抑制背蛋白抑制的基因。这些靶基因表达的差异，以及在酵母中进行的相互作用研究结果，表明Dif不能与背蛋白通常相互作用的基本螺旋-环-螺旋转录因子协同作用，因此缺乏背蛋白介导的模式形成的一个重要组成部分。
