liver-enriched gene 1a and 1b encode novel secretory proteins essential for normal liver development in zebrafish.
liver-enriched gene 1a and 1b encode novel secretory proteins essential for normal liver development in zebrafish.
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DOI：
10.1371/journal.pone.0022910
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发表时间：
2011
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：
Chang C;Hu M;Zhu Z;Lo LJ;Chen J;Peng J
肝脏富集基因1（leg 1）是斑马鱼肝脏富集基因，编码一种新蛋白。我们的初步数据表明，Leg 1可能参与早期肝脏发育。然而，到目前为止还没有关于Leg 1的详细描述。我们采用生物信息学和实验方法来研究leg 1基因结构及其在早期肝脏发育中的作用。我们发现Leg 1识别了一个新的保守蛋白超家族，其特征在于存在未知功能结构域781（DUF 781）。在斑马鱼中，leg 1有两个拷贝，即leg 1a和leg 1b。leg 1a和leg 1b都在幼虫和成体肝脏中表达，leg 1a是主要形式。通过其各自的特异性靶向其5′-UTR的吗啉代敲低Leg 1a或Leg 1b各自导致小肝脏表型，表明Leg 1a和Leg 1b对早期肝脏发育都很重要。同时，我们发现，注射leg 1-ATGMO，一种可以同时阻断Leg 1a和Leg 1b翻译的吗啉代，不仅导致小肝脏表型，而且还导致外分泌胰腺和肠管发育不良。进一步检查leg 1-ATGMO morphant与早期内胚层标志物和早期肝标志物显示，虽然总Leg 1的消耗不改变内胚层细胞的肝和胰腺命运，但它导致细胞周期停滞，导致肝、外分泌胰腺和肠的生长迟缓。最后证明了Leg 1是一种分泌蛋白。这引起了我们的兴趣，提出Leg 1可能作为一种新的分泌调节剂，对斑马鱼的肝脏和其他消化器官发育至关重要。
liver-enriched gene 1 (leg1) is a liver-enriched gene in zebrafish and encodes a novel protein. Our preliminary data suggested that Leg1 is probably involved in early liver development. However, no detailed characterization of Leg1 has been reported thus far. We undertook both bioinformatic and experimental approaches to study leg1 gene structure and its role in early liver development. We found that Leg1 identifies a new conserved protein superfamily featured by the presence of domain of unknown function 781 (DUF781). There are two copies of leg1 in zebrafish, namely leg1a and leg1b. Both leg1a and leg1b are expressed in the larvae and adult liver with leg1a being the predominant form. Knockdown of Leg1a or Leg1b by their respective morpholinos specifically targeting their 5′-UTR each resulted in a small liver phenotype, demonstrating that both Leg1a and Leg1b are important for early liver development. Meanwhile, we found that injection of leg1-ATGMO, a morpholino which can simultaneously block the translation of Leg1a and Leg1b, caused not only a small liver phenotype but hypoplastic exocrine pancreas and intestinal tube as well. Further examination of leg1-ATGMO morphants with early endoderm markers and early hepatic markers revealed that although depletion of total Leg1 does not alter the hepatic and pancreatic fate of the endoderm cells, it leads to cell cycle arrest that results in growth retardation of liver, exocrine pancreas and intestine. Finally, we proved that Leg1 is a secretory protein. This intrigued us to propose that Leg1 might act as a novel secreted regulator that is essential for liver and other digestive organ development in zebrafish.
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影响因子：
3.5
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