Department of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.
Development. 2012 Aug;139(16):3032-9. doi: 10.1242/dev.075812. Epub 2012 Jul 12.
The dorsoventral (DV) axis of the Drosophila embryo is patterned by a nuclear gradient of the Rel family transcription factor, Dorsal (Dl), that activates or represses numerous target genes in a region-specific manner. Here, we demonstrate that signaling by receptor tyrosine kinases (RTK) reduces nuclear levels and transcriptional activity of Dl, both at the poles and in the mid-body of the embryo. These effects depend on wntD, which encodes a Dl antagonist belonging to the Wingless/Wnt family of secreted factors. Specifically, we show that, via relief of Groucho- and Capicua-mediated repression, the Torso and EGFR RTK pathways induce expression of WntD, which in turn limits Dl nuclear localization at the poles and along the DV axis. Furthermore, this RTK-dependent control of Dl is important for restricting expression of its targets in both contexts. Thus, our results reveal a new mechanism of crosstalk, whereby RTK signals modulate the spatial distribution and activity of a developmental morphogen in vivo.
果蝇胚胎的背腹（DV）轴由 Rel 家族转录因子 Dorsal（Dl）的核梯度模式化，Dl 以区域特异性的方式激活或抑制许多靶基因。在这里，我们证明受体酪氨酸激酶（RTK）的信号转导会降低胚胎极和中体处 Dl 的核水平和转录活性。这些效应依赖于编码属于分泌因子 Wingless/Wnt 家族的 Dl 拮抗剂的 wntD。具体而言，我们表明，通过解除 Groucho 和 Capicua 介导的抑制，Torso 和 EGFR RTK 途径诱导 WntD 的表达，而 WntD 反过来又限制了 Dl 在极和沿 DV 轴的核定位。此外，这种 RTK 依赖性的 Dl 控制对于限制其靶基因在这两种情况下的表达是重要的。因此，我们的结果揭示了一种新的串扰机制，即 RTK 信号在体内调节发育形态发生因子的空间分布和活性。
