Cook Orna, Biehs Brian, Bier Ethan
Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0349, USA.
Development. 2004 May;131(9):2113-24. doi: 10.1242/dev.01100. Epub 2004 Apr 8.
The stereotyped pattern of Drosophila wing veins is determined by the action of two morphogens, Hedgehog (Hh) and Decapentaplegic (Dpp), which act sequentially to organize growth and patterning along the anterior-posterior axis of the wing primordium. An important unresolved question is how positional information established by these morphogen gradients is translated into localized development of morphological structures such as wing veins in precise locations. In the current study, we examine the mechanism by which two broadly expressed Dpp signaling target genes, optomotor-blind (omb) and brinker (brk), collaborate to initiate formation of the fifth longitudinal (L5) wing vein. omb is broadly expressed at the center of the wing disc in a pattern complementary to that of brk, which is expressed in the lateral regions of the disc and represses omb expression. We show that a border between omb and brk expression domains is necessary and sufficient for inducing L5 development in the posterior regions. Mosaic analysis indicates that brk-expressing cells produce a short-range signal that can induce vein formation in adjacent omb-expressing cells. This induction of the L5 primordium is mediated by abrupt, which is expressed in a narrow stripe of cells along the brk/omb border and plays a key role in organizing gene expression in the L5 primordium. Similarly, in the anterior region of the wing, brk helps define the position of the L2 vein in combination with another Dpp target gene, spalt. The similar mechanisms responsible for the induction of L5 and L2 development reveal how boundaries set by dosage-sensitive responses to a long-range morphogen specify distinct vein fates at precise locations.
果蝇翅脉的定型模式由两种形态发生素——刺猬蛋白（Hh）和五体不全蛋白（Dpp）的作用所决定，它们依次作用以沿翅原基的前后轴组织生长和模式形成。一个重要的未解决问题是，由这些形态发生素梯度建立的位置信息如何转化为精确位置上形态结构（如翅脉）的局部发育。在当前的研究中，我们研究了两个广泛表达的Dpp信号靶基因——视动盲（omb）和边缘（brk）协同启动第五纵脉（L5）形成的机制。omb在翅盘中心广泛表达，其模式与brk互补，brk在翅盘的外侧区域表达并抑制omb的表达。我们发现omb和brk表达域之间的边界对于诱导后部区域的L5发育是必要且充分的。镶嵌分析表明，表达brk的细胞产生一种短程信号，该信号可诱导相邻的表达omb的细胞形成翅脉。L5原基的这种诱导由abrupt介导，abrupt在沿着brk/omb边界的窄条细胞中表达，并在组织L5原基中的基因表达中起关键作用。同样，在翅的前部区域，brk与另一个Dpp靶基因spalt共同作用，有助于确定L2翅脉的位置。负责诱导L5和L2发育的相似机制揭示了对远程形态发生素的剂量敏感反应所设定的边界如何在精确位置指定不同的翅脉命运。
