Local inhibition and long-range enhancement of Dpp signal transduction by Sog
Local inhibition and long-range enhancement of Dpp signal transduction by Sog
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DOI：
10.1038/18892
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发表时间：
1999-04-01
期刊：
影响因子：
64.8
通讯作者：
Levine, M
中科院分区：
文献类型：
--
作者：
Ashe, HL;Levine, M
细胞外信号分子的梯度可以指定发育中基因活性的不同阈值。果蝇胚胎背侧外胚层的DPP活性梯度将其分为羊膜和背侧外胚层(1，2)，这种梯度的形成需要短原肠形成蛋白(SOG)和类固醇蛋白(4)(TLD)。SOG已被提出与DPP(5)或相关的配体螺杆(6，7)形成抑制复合体，并随后被蛋白酶TLD(5)处理。矛盾的是，羊膜浆膜的形成似乎需要SOG(8)，这是由DPP信号活动峰值(1，2)指定的。在这里，我们证明了使用偶数跳过的条纹-2增强子(9)的SAG的错误表达在一个突变背景中重新分布了DPP信号，其中NPP在整个胚胎中表达，DPP活性在SOG条纹附近减弱，峰值DPP信号在远离该条纹的地方被检测到。然而，栓系形式的SOG抑制局部DPP活性而不增强远距离的DPP活性，这表明SOG的扩散可能是增强DPP活性和随后的羊膜形成所必需的，SOG对DPP活性的远程刺激需要TLD，而SOG介导的DPP抑制不需要TLD，而异源DPP抑制剂Noggin(10)抑制DPP信号转导但不能增强DPP活性。这些结果表明了一种不寻常的策略来产生生长因子活性的梯度阈值，根据该策略，SOG及其蛋白酶指定峰值DPP信号，而不是SOG的局部来源。
Extracellular gradients of signalling molecules can specify different thresholds of gene activity in development. A gradient of Decapentaplegic (Dpp) activity subdivides the dorsal ectoderm of the Drosophila embryo into amnioserosa and dorsal epidennis(.1,2) The proteins Short gastrulation(3) (Sog) and Tolloid(4) (Tld) are required to shape this gradient. Sog has been proposed to form an inhibitory complex with either Dpp(5) or the related ligand Screw(6,7), and is subsequently processed by the protease Tld(5). Paradoxically, Sog appears to be required for amnioserosa formation(8), which is specified by peak Dpp signalling activity(1,2). Here we show that the misexpression of sag using the even-skipped stripe-2 enhancer(9) redistributes Dpp signalling in a mutant background in which npp is expressed throughout the embryo, Dpp activity is diminished near the Sog stripe and peak Dpp signalling is detected far from this stripe. However, a tethered form of Sog suppresses local Dpp activity without augmenting Dpp activity at a distance, indicating that diffusion of Sog may be required for enhanced Dpp activity and consequent amnioserosa formation, The long-distance stimulation of Dpp activity by Sog requires Tld, whereas Sog-mediated inhibition of Dpp does not The heterologous Dpp inhibitor Noggin(10) inhibits Dpp signalling but fails to augment Dpp activity. These results suggest an unusual strategy for generating a gradient threshold of growth-factor activity, whereby Sog and its protease specify peak Dpp signalling far from a localized source of Sog.