Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish.
Abnormal nuclear pore formation triggers apoptosis in the intestinal epithelium of elys-deficient zebrafish.
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DOI：
10.1053/j.gastro.2008.11.012
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发表时间：
2009-03
期刊：
影响因子：
29.4
通讯作者：
Heath JK
中科院分区：
文献类型：
--
作者：
de Jong-Curtain TA;Parslow AC;Trotter AJ;Hall NE;Verkade H;Tabone T;Christie EL;Crowhurst MO;Layton JE;Shepherd IT;Nixon SJ;Parton RG;Zon LI;Stainier DY;Lieschke GJ;Heath JK
乙基亚硝基脲（ENU）诱变产生的斑马鱼突变体提供了一个强大的工具，解剖发育过程中的遗传调控，包括器官发生。斑马鱼的一个突变体，flo乐天在78 hpf时显示出肠、肝、胰腺和眼睛形成的明显缺陷。在这项研究中，我们试图确定flo中潜在的突变基因，并将遗传损伤与其表型联系起来。采用定位克隆技术对flo突变进行定位。采用组织学、免疫细胞化学、溴脱氧尿苷掺入分析、共聚焦显微镜和电子显微镜对胚胎进行亚细胞鉴定。flo中的分子损伤是elys（来自卵黄囊的胚胎大分子）基因中的无义突变，其编码缺乏Elys C-末端AT-钩DNA结合结构域的严重截短的蛋白。最近，ELYS已被证明在核孔组装中起着关键的，迄今未被怀疑的作用。虽然elys mRNA在早期斑马鱼发育过程中广泛表达，但直到24 hpf，母体表达的elys mRNA的持续性避免了flo中广泛的早期缺陷。从72 hpf开始，elys mRNA表达仅限于增殖组织，包括肠上皮、胰腺、肝脏和眼睛。这些组织中的细胞显示核孔形成中断;最终肠上皮细胞发生凋亡。我们的研究结果表明，Elys调节消化器官的形成。
Zebrafish mutants generated by ethylnitrosourea (ENU)-mutagenesis provide a powerful tool for dissecting the genetic regulation of developmental processes, including organogenesis. One zebrafish mutant, “flotte lotte” (flo), displays striking defects in intestinal, liver, pancreas and eye formation at 78hpf. In this study we sought to identify the underlying mutated gene in flo and link the genetic lesion to its phenotype. Positional cloning was employed to map the flo mutation. Sub-cellular characterization of flo embryos was achieved using histology, immunocytochemistry, bromodeoxyuridine incorporation analysis, confocal and electron microscopy. The molecular lesion in flo is a nonsense mutation in the elys (embryonic large molecule derived from yolk sac) gene which encodes a severely truncated protein lacking the Elys C-terminal AT-hook DNA binding domain. Recently, ELYS has been shown to play a critical, and hitherto unsuspected, role in nuclear pore assembly. Though elys mRNA is expressed broadly during early zebrafish development, widespread early defects in flo are circumvented by the persistence of maternally-expressed elys mRNA until 24hpf. From 72hpf, elys mRNA expression is restricted to proliferating tissues, including the intestinal epithelium, pancreas, liver and eye. Cells in these tissues display disrupted nuclear pore formation; ultimately intestinal epithelial cells undergo apoptosis. Our results demonstrate that Elys regulates digestive organ formation.
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影响因子：
2.1
作者：
Okita, K;Kiyonari, H;Taga, T
通讯作者：
Taga, T
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2.5
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KIMMEL, CB;BALLARD, WW;SCHILLING, TF
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SCHILLING, TF
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32.4
作者：
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Fontoura, BMA
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2.7
作者：
Ng, ANY;de Jong-Curtain, TA;Heath, JK
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Heath, JK
影响因子：
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作者：
Ober, Elke A.;Verkade, Heather;Stainier, Didier Y. R.
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Stainier, Didier Y. R.