Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter
Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter
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DOI：
10.1016/j.yexcr.2006.01.016
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发表时间：
2006-05-15
影响因子：
3.7
通讯作者：
Gong, Zhiyuan
中科院分区：
文献类型：
--
作者：
Wan, Haiyan;Korzh, Suitlana;Gong, Zhiyuan
与我们所知道的内分泌胰腺的发育相反，外分泌胰腺的形成仍然知之甚少。为了建立一个动物模型，允许观察外分泌细胞分化，增殖和形态发生在活的动物，我们使用斑马鱼弹性蛋白酶A（elaA）的调节序列开发转基因斑马鱼，显示高度特异性的外分泌胰腺表达GFP在幼虫和成人。通过跟踪GFP表达，我们发现胰腺在早期发育中是一个相对紧凑的器官，后来沿着肠向后沿着。通过将elaA：gfp转基因转移到缺乏Hedgehog信号的慢肌缺失突变体中，我们进一步表明Hedgehog信号是外分泌形态发生所需的，但不是细胞分化所需的。我们还将吗啉代敲低和毒素介导的细胞消融方法应用于该转基因系。我们发现，胰腺外分泌的发展是胰岛-1依赖。在弹性蛋白酶A启动子下注射白喉毒素A（DTA）构建体导致外分泌细胞的选择性消融，而内分泌细胞和其他内胚层衍生物（肝和肠）不受影响。因此，我们的工作表明，新的转基因株系提供了一个有用的实验工具，分析外分泌胰腺的发展。(c)2006年爱思唯尔公司All rights reserved.
In contrast to what we know on development of endocrine pancreas, the formation of exocrine pancreas remains poorly understood. To create an animal model that allows observation of exocrine cell differentiation, proliferation, and morphogenesis in living animals, we used the zebrafish elastaseA (elaA) regulatory sequence to develop transgenic zebrafish that display highly specific exocrine pancreas expression of GFP in both larvae and adult. By following GFP expression, we found that the pancreas in early development was a relatively compact organ and later extended posterior along the intestine. By transferring the elaA:gfp transgene into slow muscle omitted mutant that is deficient in receiving Hedgehog signals, we further showed that Hedgehog signaling is required for exocrine morphogenesis but not for cell differentiation. We also applied the morpholino knockdown and toxin-mediated cell ablation approaches to this transgenic line. We showed that the development of exocrine pancreas is Islet-1 dependent. Injection of the diphtheria toxin A (DTA) construct under the elastaseA promoter resulted in selective ablation of exocrine cells while the endocrine cells and other endodermal derivatives (liver and intestine) were not affected. Thus, our works demonstrated the new transgenic line provided a useful experimental tool in analyzing exocrine pancreas development. (c) 2006 Elsevier Inc. All rights reserved.