The effects of methylmercury on Notch signaling during embryonic neural development in Drosophila melanogaster.
The effects of methylmercury on Notch signaling during embryonic neural development in Drosophila melanogaster.
复制标题
DOI：
10.1016/j.tiv.2011.12.014
复制
发表时间：
2012-04
影响因子：
3.2
通讯作者：
Rand, M. D.
中科院分区：
文献类型：
--
作者：
Engel, G. L.;Delwig, A.;Rand, M. D.
甲基汞（MeHg）是一种普遍存在的有毒物质，以发育中的胎儿神经系统为目标。甲基汞与Notch信号通路相互作用，Notch信号通路是正常发育所需的高度保守的细胞间信号机制。Notch信号传导通过激活果蝇中分裂增强子（E（spl））基因座中的基因来传递。我们之前已经证明，急性高剂量的MeHg会上调果蝇神经源性C6细胞中的几个E（spl）基因。此外，甲基汞对E（spl）的诱导可以独立于Notch受体本身而发生。我们现在发现，甲基汞，不像无机汞（氯化汞），优先上调E（spl）mδ和E（spl）mγ在果蝇C6细胞。这与δ配体诱导的Notch信号传导不同，其中未观察到E（spl）mδ的诱导。甲基汞也被认为能特异性地上调果蝇胚胎中的E（spl）mδ，而氯化汞则没有这种作用。此外，用甲基汞处理胚胎导致节间神经（ISN）轴突生长的一致失败。这种ISN表型通过Notch途径的遗传激活而部分复制，但不能通过增加E（spl）mδ的表达而复制。这些数据表明Notch信号传导和E（spl）mδ靶基因在甲基汞毒性中的作用，然而，E（spl）mδ在该系统中的作用位点仍有待阐明。
Methylmercury (MeHg) is a ubiquitous toxicant that targets the developing fetal nervous system. MeHg interacts with the Notch signaling pathway, a highly-conserved intercellular signaling mechanism required for normal development. Notch signaling is conveyed by activation of the genes in the Enhancer of Split (E(spl)) locus in Drosophila. We have previously shown that acute high doses of MeHg upregulate several E(spl) genes in Drosophila neural-derived C6 cells. Furthermore, MeHg induction of E(spl) can occur independent of the Notch receptor itself. We now show that MeHg, unlike inorganic mercury (HgCl2), preferentially upregulates E(spl)mδ and E(spl)mγ in Drosophila C6 cells. This is distinct from Delta ligand-induced Notch signaling in which no induction of E(spl)mδ is seen. MeHg is also seen to specifically upregulate E(spl)mδ in Drosophila embryos where HgCl2 showed no such effect. Additionally, treatment of embryos with MeHg caused a consistent failure in axonal outgrowth of the intersegmental nerve (ISN). This ISN phenotype was partially replicated by genetic activation of the Notch pathway, but was not replicated by increasing expression of E(spl)mδ. These data suggest a role for Notch signaling and the E(spl)mδ target gene in MeHg toxicity, however, the site of action for E(spl)mδ in this system remains to be elucidated.
登录
查看更多内容
影响因子：
3.8
作者：
Mahapatra, Cecon T.;Bond, Jeffrey;Rand, Matthew D.
通讯作者：
Rand, Matthew D.
影响因子：
11.4
作者：
PREISS, A;HARTLEY, DA;ARTAVANISTSAKONAS, S
通讯作者：
ARTAVANISTSAKONAS, S
影响因子：
2.6
作者：
Wurmbach, E;Wech, I;Preiss, A
通讯作者：
Preiss, A
影响因子：
64.8
作者：
Graveley BR;Brooks AN;Carlson JW;Duff MO;Landolin JM;Yang L;Artieri CG;van Baren MJ;Boley N;Booth BW;Brown JB;Cherbas L;Davis CA;Dobin A;Li R;Lin W;Malone JH;Mattiuzzo NR;Miller D;Sturgill D;Tuch BB;Zaleski C;Zhang D;Blanchette M;Dudoit S;Eads B;Green RE;Hammonds A;Jiang L;Kapranov P;Langton L;Perrimon N;Sandler JE;Wan KH;Willingham A;Zhang Y;Zou Y;Andrews J;Bickel PJ;Brenner SE;Brent MR;Cherbas P;Gingeras TR;Hoskins RA;Kaufman TC;Oliver B;Celniker SE
通讯作者：
Celniker SE
影响因子：
14.9
作者：
Tweedie S;Ashburner M;Falls K;Leyland P;McQuilton P;Marygold S;Millburn G;Osumi-Sutherland D;Schroeder A;Seal R;Zhang H;FlyBase Consortium
通讯作者：
FlyBase Consortium