Remodeling the exocrine pancreas at metamorphosis in Xenopus laevis
Remodeling the exocrine pancreas at metamorphosis in Xenopus laevis
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DOI：
10.1073/pnas.0803569105
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发表时间：
2008-07-01
影响因子：
11.1
通讯作者：
Brown, Donald D.
中科院分区：
文献类型：
--
作者：
Mukhi, Sandeep;Mao, Jinzhe;Brown, Donald D.
在变态阶段，非洲爪蟾蝌蚪外分泌胰腺的重塑分为两个阶段。在变态的高潮，甲状腺激素（TH）诱导整个外分泌胰腺去分化到祖细胞状态。器官缩小到原来大小的20%，大约40%的细胞死亡。腺泡细胞失去它们的酶原颗粒和大约75%的RNA。编码外分泌特异性蛋白的mrna（包括转录因子Ptf1a）在高潮时几乎完全消失，而与祖细胞分化有关的基因PDX-1、Notch-1和Hes-1则被激活。在自发性变态结束时，当内源性TH达到低水平时，胰腺开始再分化。外源TH诱导去分化期，但不诱导再分化期。蝌蚪的胰腺缺乏成熟的导管系统，而成熟的导管系统存在于成年脊椎动物的胰腺中，包括青蛙。表达由弹性蛋白酶启动子控制的显性负型TH受体的转基因蝌蚪的外分泌胰腺对TH具有抗性。他们不收缩时，受到TH。它们的腺泡细胞在高潮时不会去分化，也不会下调外分泌特异性基因或激活Notch-1和Hes-1。甚至在蜕变2个月后，这些青蛙还没有发育出成熟的导管系统，腺泡细胞排列异常。蝌蚪腺泡细胞在顶点的th依赖性去分化是形成成熟青蛙胰腺的必要步骤。
At metamorphosis the Xenopus laevis tadpole exocrine pancreas remodels in two stages. At the climax of metamorphosis thyroid hormone (TH) induces dedifferentiation of the entire exocrine pancreas to a progenitor state. The organ shrinks to 20% of its size, and approximate to 40% of its cells die. The acinar cells lose their zymogen granules and approximate to 75% of their RNA. The mRNAs that encode exocrine-specific proteins (including the transcription factor Ptf1a) undergo almost complete extinction at climax, whereas PDX-1, Notch-1, and Hes-1, genes implicated in differentiation of the progenitor cells, are activated. At the end of spontaneous metamorphosis when the endogenous TH has reached a low level, the pancreas begins to redifferentiate. Exogenous TH induces the dedifferentiation phase but not the redifferentation phase. The tadpole pancreas lacks the mature ductal system that is found in adult vertebrate pancreases, including the frog. Exocrine pancreases of transgenic tadpoles expressing a dominant negative form of the TH receptor controlled by the elastase promoter are resistant to TH. They do not shrink when subjected to TH. Their acinar cells do not dedifferentiate at climax, nor do they down-regulate exocrine-specific genes or activate Notch-1, and Hes-1. Even 2 months after metamorphosis these frogs have not developed a mature ductal system and the acinar cells are abnormally arranged. The TH-dependent dedifferentiation of the tadpole acinar cells at climax is a necessary step in the formation of a mature frog pancreas.