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RTK 信号调控 Dorsal 梯度。

RTK signaling modulates the Dorsal gradient.

机构信息

Department of Developmental Biology and Cancer Research, IMRIC, Faculty of Medicine, The Hebrew University, Jerusalem 91120, Israel.

出版信息

Development. 2012 Aug;139(16):3032-9. doi: 10.1242/dev.075812. Epub 2012 Jul 12.

Abstract

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.

摘要

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。

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