Def functions as a cell autonomous factor in organogenesis of digestive organs in zebrafish.
Def functions as a cell autonomous factor in organogenesis of digestive organs in zebrafish.
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DOI：
10.1371/journal.pone.0058858
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Tao T;Shi H;Huang D;Peng J
消化器官起源于内胚层。消化系统的形态发生受到多种因素的精确控制，这些因素决定了细胞的命运和行为，从而使特定的消化器官及时在正确的位置形成，并发育成正确的大小和结构。我们先前发现消化器官扩展因子（def）是一个在肝脏、胰腺和肠中表达丰富的基因。defhi 429突变体中def功能丧失导致消化器官发育不全，部分原因是与p53通路相关的基因表达改变。然而，Def参与消化器官发生的分子机制仍不清楚。例如，目前尚不清楚Def是否调节特定器官中的特定途径。为了解决这个问题，我们产生了四个独立的Tg（fabp 10a：def）转基因鱼线，过表达的Def特异性在肝脏中。我们对转基因株系Tg-I进行了遗传学、分子生物学和组织学研究。我们发现，Tg-I恢复了肝脏，但没有外分泌胰腺和肠道发育的defhi 429突变体。然而，Tg-I成鱼在野生型（WT）的背景下表现出降低的肝体比和所有四个转基因系赋予异常的肝内结构。微阵列数据分析表明，某些特定的功能途径的影响，在肝脏的Tg-I。这些结果表明，在早期肝脏发育过程中，Def以细胞自主的方式发挥作用，异常的Def蛋白表达可能导致正常成人肝脏结构完整性的破坏。
Digestive organs originate from the endoderm. Morphogenesis of the digestive system is precisely controlled by multiple factors that dictate the cell fate and behavior so that the specific digestive organs are timely formed in the right place and develop into right size and structure. We showed previously that digestive organ expansion factor (def) is a gene whose expression is enriched in the liver, pancreas and intestine. Loss-of-function of def in the defhi429 mutant confers hypoplastic digestive organs partly due to alteration of expression of genes related to the p53 pathway. However, the molecular mechanism for the involvement of Def in the organogenesis of digestive organs is still largely unknown. For example, it is not known whether Def regulates specific pathways in a specific organ. To address this question, we generated four independent Tg(fabp10a:def) transgenic fish lines which over-expressed Def specifically in the liver. We characterized Tg-I, one of the transgenic lines, in detail with genetic, molecular and histological approaches. We found that Tg-I restored the liver but not exocrine pancreas and intestine development in the defhi429 mutant. However, Tg-I adult fish in the wild type (WT) background exhibits reduced liver-to-body ratio and all four transgenic lines conferred abnormal intrahepatic structure. Microarray data analysis showed that certain specific functional pathways were affected in the liver of Tg-I. These results demonstrate that Def functions in a cell autonomous manner during early liver development and aberrant Def protein expression might lead to disruption of the structural integrity of a normal adult liver.
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