Gao Q, Finkelstein R
University of Pennsylvania School of Medicine, Department of Neuroscience, Philadelphia PA 19104, USA.
Development. 1998 Nov;125(21):4185-93. doi: 10.1242/dev.125.21.4185.
The Bicoid (Bcd) morphogen establishes the head and thorax of the Drosophila embryo. Bcd activates the transcription of identified target genes in the thoracic segments, but its mechanism of action in the head remains poorly understood. It has been proposed that Bcd directly activates the cephalic gap genes, which are the first zygotic genes to be expressed in the head primordium. It has also been suggested that the affinity of Bcd-binding sites in the promoters of Bcd target genes determines the posterior extent of their expression (the Gene X model). However, both these hypotheses remain untested. Here, we show that a small regulatory region upstream of the cephalic gap gene orthodenticle (otd) is sufficient to recapitulate early otd expression in the head primordium. This region contains two control elements, each capable of driving otd-like expression. The first element has consensus Bcd target sites that bind Bcd in vitro and are necessary for head-specific expression. As predicted by the Gene X model, this element has a relatively low affinity for Bcd. Surprisingly, the second regulatory element has no Bcd sites. Instead, it contains a repeated sequence motif similar to a regulatory element found in the promoters of otd-related genes in vertebrates. Our study is the first demonstration that a cephalic gap gene is directly regulated by Bcd. However, it also shows that zygotic gene expression can be targeted to the head primordium without direct Bcd regulation.
双尾（Bcd）形态发生素确立了果蝇胚胎的头部和胸部。Bcd激活了胸段中已确定的靶基因的转录，但其在头部的作用机制仍知之甚少。有人提出，Bcd直接激活头部间隙基因，这些基因是在头部原基中最早表达的合子基因。也有人认为，Bcd靶基因启动子中Bcd结合位点的亲和力决定了它们表达的后部范围（基因X模型）。然而，这两种假设都尚未得到验证。在这里，我们表明，头部间隙基因正齿（otd）上游的一个小调控区域足以重现头部原基中otd的早期表达。该区域包含两个控制元件，每个元件都能够驱动类似otd的表达。第一个元件具有一致的Bcd靶位点，这些位点在体外与Bcd结合，并且是头部特异性表达所必需的。正如基因X模型所预测的，该元件对Bcd的亲和力相对较低。令人惊讶的是，第二个调控元件没有Bcd位点。相反，它包含一个重复的序列基序，类似于在脊椎动物otd相关基因启动子中发现的一个调控元件。我们的研究首次证明了一个头部间隙基因受到Bcd的直接调控。然而，它也表明，合子基因的表达可以在没有Bcd直接调控的情况下靶向头部原基。
