Ciechanska Ewa, Dansereau David A, Svendsen Pia C, Heslip Tim R, Brook William J
Genes and Development Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada.
Genome. 2007 Aug;50(8):693-705. doi: 10.1139/g07-043.
The segmentation of the proximal-distal axis of the Drosophila melanogaster leg depends on the localized activation of the Notch receptor. The expression of the Notch ligand genes Serrate and Delta in concentric, segmental rings results in the localized activation of Notch, which induces joint formation and is required for the growth of leg segments. We report here that the expression of Serrate and Delta in the leg is regulated by the transcription factor genes dAP-2 and defective proventriculus. Previous studies have shown that Notch activation induces dAP-2 in cells distal and adjacent to the Serrate/Delta domain of expression. We find that Serrate and Delta are ectopically expressed in dAP-2 mutant legs and that Serrate and Delta are repressed by ectopic expression of dAP-2. Furthermore, Serrate is induced cell-autonomously in dAP-2 mutant clones in many regions of the leg. We also find that the expression of a defective proventriculus reporter overlaps with dAP-2 expression and is complementary to Serrate expression in the tarsal segments. Ectopic expression of defective proventriculus is sufficient to block joint formation and Serrate and Delta expression. Loss of defective proventriculus results in localized, ectopic Serrate expression and the formation of ectopic joints with reversed polarity. Thus, in tarsal segments, dAP-2 and defective proventriculus are necessary for the correct proximal and distal boundaries of Serrate expression and repression of Serrate by defective proventriculus contributes to tarsal segment asymmetry. The repression of the Notch ligand genes Serrate and Delta by the Notch target gene dAP-2 may be a pattern-refining mechanism similar to those acting in embryonic segmentation and compartment boundary formation.
黑腹果蝇腿部近-远轴的分割取决于Notch受体的局部激活。Notch配体基因Serrate和Delta在同心的节段环中表达，导致Notch的局部激活，这诱导关节形成并且是腿部节段生长所必需的。我们在此报告，腿部中Serrate和Delta的表达受转录因子基因dAP-2和缺陷型前胃的调控。先前的研究表明，Notch激活在表达Serrate/Delta结构域远端和相邻的细胞中诱导dAP-2。我们发现Serrate和Delta在dAP-2突变体腿部异位表达，并且Serrate和Delta被dAP-2的异位表达所抑制。此外，Serrate在腿部许多区域的dAP-2突变体克隆中自主诱导表达。我们还发现缺陷型前胃报告基因的表达与dAP-2的表达重叠，并且在跗节段中与Serrate的表达互补。缺陷型前胃的异位表达足以阻断关节形成以及Serrate和Delta的表达。缺陷型前胃的缺失导致局部异位Serrate表达以及极性反转的异位关节形成。因此，在跗节段中，dAP-2和缺陷型前胃对于Serrate表达的正确近侧和远侧边界是必需的，并且缺陷型前胃对Serrate的抑制有助于跗节段不对称。Notch靶基因dAP-2对Notch配体基因Serrate和Delta的抑制可能是一种类似于在胚胎分割和隔室边界形成中起作用的模式细化机制。
