Down-regulation of Notch target gene expression by Suppressor of deltex
Down-regulation of Notch target gene expression by Suppressor of deltex
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DOI：
10.1016/s0012-1606(02)00086-6
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发表时间：
2003-03-15
影响因子：
2.7
通讯作者：
Baron, M
中科院分区：
文献类型：
--
作者：
Mazaleyrat, SL;Fostier, M;Baron, M
在果蝇中，deltex 抑制子 (Su(dx)) 突变表现出类似于 Notch 功能获得等位基因的翼静脉间隙表型。因此，Su(dx) 蛋白可能充当 Notch 的负调节因子，但其对实际 Notch 信号传导水平的活性尚未得到证实。在这里，我们表明 Su(dx) 确实在体内、Notch 靶基因上游和不同的发育环境中调节 Notch 信号传导水平，包括在腿部关节形成中以前未知的作用。 Su(dx) 的过表达能够阻断 Notch 的内源活性以及由细胞内 Notch 结合蛋白 Deltex 的过表达诱导的异位 Notch 信号传导。此外，利用 Su(dx)(sp) 等位基因的条件表型，我们发现 Su(dx) 活性丧失后，E(spl)mbeta 表达迅速上调，E(spl)mbeta 表达是翼静脉发育过程中 Notch 信号激活的直接目标。虽然 Su(dx) 成虫翼静脉表型相当轻微，仅影响静脉的远端，但我们表明 Su(dx) 活性丧失的最初后果比之前想象的更为严重。通过时间过程实验，我们表明表型通过反馈调节进行缓冲，说明信号网络如何使发育对扰动具有鲁棒性。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
In Drosophila, Suppressor of deltex (Su(dx)) mutations display a wing vein gap phenotype resembling that of Notch gain of function alleles. The Su(dx) protein may therefore act as a negative regulator of Notch but its activity on actual Notch signalling levels has not been demonstrated. Here we show that Su(dx) does regulate the level of Notch signalling in vivo, upstream of Notch target genes and in different developmental contexts, including a previously unknown role in leg joint formation. Overexpression of Su(dx) was capable of blocking both the endogenous activity of Notch and the ectopic Notch signalling induced by the overexpression of Deltex, an intracellular Notch binding protein. In addition, using the conditional phenotype of the Su(dx)(sp) allele, we show that loss of Su(dx) activity is rapidly followed by an up-regulation of E(spl)mbeta expression, the immediate target of Notch signal activation during wing vein development. While Su(dx) adult wing vein phenotypes are quite mild, only affecting the distal tips of the veins, we show that the initial consequence of loss of Su(dx) activity is more severe than previously thought. Using a time-course experiment we show that the phenotype is buffered by feedback regulation illustrating how signalling networks can make development robust to perturbation. (C) 2003 Elsevier Science (USA). All rights reserved.