Bellaïche Y, Bandyopadhyay R, Desplan C, Dostatni N
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Development. 1996 Nov;122(11):3499-508. doi: 10.1242/dev.122.11.3499.
Bicoid (Bcd) is a maternal morphogen responsible for patterning the head and thorax of the Drosophila embryo. Correct specification of head structure, however, requires the activity of the Torso receptor tyrosine kinase cascade, which also represses expression of Bcd targets at the most anterior tip of the embryo. Here, we investigate the role of both the homeodomain (HD) and the activation domain of Bcd in the anterior repression of its targets. When a Bcd mutant protein whose HD has been replaced by the Gal4 DNA-binding domain is expressed in early embryos, a reporter gene driven by Gal4 DNA-binding sites is first activated in an anterior domain and then repressed from the anterior pole. The down-regulation of Bcd-Gal4 activity requires torso function but does not depend on endogenous bcd activity, indicating that the Bcd protein alone and none of its targets is required to mediate the effect of torso. Functional analysis of a chimeric protein, whose activation domain has been replaced by a generic activation domain, indicates that the activation domain of Bcd is also not specifically required for its down-regulation by Torso. We propose that Torso does not affect the ability of Bcd to bind DNA, but instead directs modification of Bcd or of a potential Bcd co-factor, which renders the Bcd protein unable to activate transcription.
双尾（Bcd）是一种母体形态发生素，负责果蝇胚胎头部和胸部的模式形成。然而，头部结构的正确特化需要躯干受体酪氨酸激酶级联反应的活性，该级联反应也会抑制胚胎最前端Bcd靶标的表达。在这里，我们研究了Bcd的同源结构域（HD）和激活结构域在其靶标前侧抑制中的作用。当一个HD被Gal4 DNA结合结构域取代的Bcd突变蛋白在早期胚胎中表达时，由Gal4 DNA结合位点驱动的报告基因首先在前侧区域被激活，然后从前极被抑制。Bcd-Gal4活性的下调需要躯干功能，但不依赖于内源性bcd活性，这表明仅Bcd蛋白及其靶标均不需要介导躯干的作用。对一种激活结构域被通用激活结构域取代的嵌合蛋白的功能分析表明，Bcd的激活结构域对于其被躯干下调也不是特异性必需的。我们提出，躯干并不影响Bcd与DNA结合的能力，而是直接对Bcd或潜在的Bcd辅因子进行修饰，从而使Bcd蛋白无法激活转录。
