Hays R, Buchanan K T, Neff C, Orenic T V
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
Development. 1999 Jul;126(13):2891-9. doi: 10.1242/dev.126.13.2891.
During development, global patterning events initiate signal transduction cascades which gradually establish an array of individual cell fates. Many of the genes which pattern Drosophila are expressed throughout development and specify diverse cell types by creating unique local environments which establish the expression of locally acting genes. This process is exemplified by the patterning of leg microchaete rows. hairy (h) is expressed in a spatially restricted manner in the leg imaginal disc and functions to position adult leg bristle rows by negatively regulating the proneural gene achaete, which specifies sensory cell fates. While much is known about the events that partition the leg imaginal disc and about sensory cell differentiation, the mechanisms that refine early patterning events to the level of individual cell fate specification are not well understood. We have investigated the regulation of h expression along the dorsal/ventral (D/V) axis of the leg adjacent to the anterior/posterior (A/P) compartment boundary and have found that it requires input from both D/V and A/P patterning mechanisms. Expression of the D/V axis h stripe (D/V-h) is controlled by dorsal- and ventral-specific enhancer elements which are targets of Decapentaplegic (Dpp) and Wingless (Wg) signaling, respectively, but which are also dependent on Hedgehog (Hh) signaling for activation. D/V-h expression is lost in smoothened mutant clones and is specifically activated by exogenously supplied Cubitus interruptus (Ci). D/V-h expression is also lost in clones deficient for Dpp and Wg signaling, but ectopic activation of D/V-h by Dpp and Wg is limited to the A/P compartment boundary where endogenous levels of full-length Ci are high. We propose that D/V-h expression is regulated in a non-linear pathway in which Ci plays a dual role. In addition to serving as an upstream activator of Dpp and Wg, Ci acts combinatorially with them to activate D/V-h expression.
在发育过程中，全局模式形成事件启动信号转导级联反应，逐渐建立一系列个体细胞命运。许多参与果蝇模式形成的基因在整个发育过程中表达，并通过创造独特的局部环境来指定多种细胞类型，这些局部环境决定了局部作用基因的表达。腿部微刚毛排的模式形成就是这一过程的例证。hairy（h）基因在腿部成虫盘以空间限制的方式表达，通过负调控指定感觉细胞命运的原神经基因achaete来定位成虫腿部刚毛排。虽然我们对划分腿部成虫盘的事件以及感觉细胞分化了解很多，但将早期模式形成事件细化到个体细胞命运指定水平的机制尚不清楚。我们研究了h基因在腿部背/腹（D/V）轴上靠近前/后（A/P）隔室边界处的表达调控，发现它需要D/V和A/P模式形成机制的输入。D/V轴h条纹（D/V-h）的表达由背侧和腹侧特异性增强子元件控制，它们分别是Decapentaplegic（Dpp）和Wingless（Wg）信号通路的靶标，但也依赖于Hedgehog（Hh）信号通路的激活。D/V-h的表达在smoothened突变克隆中缺失，并被外源提供的Cubitus interruptus（Ci）特异性激活。D/V-h的表达在缺乏Dpp和Wg信号通路的克隆中也会缺失，但Dpp和Wg对D/V-h的异位激活仅限于A/P隔室边界，此处全长Ci的内源性水平较高。我们提出D/V-h的表达通过一种非线性途径进行调控，其中Ci发挥双重作用。除了作为Dpp和Wg的上游激活剂外，Ci还与它们协同作用以激活D/V-h的表达。
