The PAF1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish.
The PAF1 complex component Leo1 is essential for cardiac and neural crest development in zebrafish.
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DOI：
10.1016/j.ydbio.2010.02.020
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发表时间：
2010-05-01
影响因子：
2.7
通讯作者：
Chen, Jau-Nian
中科院分区：
文献类型：
--
作者：
Nguyen, Catherine T.;Langenbacher, Adam;Hsieh, Michael;Chen, Jau-Nian
Leo 1是聚合酶相关因子1（PAF 1）复合物的一个组成部分，PAF 1是一种进化上保守的蛋白质复合物，参与基因转录调控和染色质重塑。leo1在脊椎动物胚胎发生中的作用以前没有被研究过。在这里，我们报告说，斑马鱼leo1编码的核蛋白，具有类似的分子结构Leo1蛋白从其他物种。通过遗传筛选，我们发现了一个leo1基因缺陷的斑马鱼突变体。截短的Leo1LA1186蛋白缺乏核定位信号，主要分布在细胞质中。表型分析表明，虽然原始心管的初始图案不受影响leo1LA1186突变胚胎，在房室边界的心肌细胞的分化是异常的，这表明需要Leo1在心脏分化。此外，leo1LA 1186突变体中神经嵴衍生细胞标记物（如crestin、gch 2、dct和mitfa）的表达水平大大降低，表明Leo 1在维持神经嵴群体中的需求。与这一发现相一致，黑素细胞和黄色素细胞的人口严重减少，颅面软骨几乎检测不到，MBP阳性神经胶质细胞在leo1LA1186突变体中不存在后三天的发展。总之，这些结果提供了第一个遗传证据的要求Leo1在心脏和神经嵴细胞群体的发展。
Leo1 is a component of the Polymerase-Associated Factor 1 (PAF1) complex, an evolutionarily conserved protein complex involved in gene transcription regulation and chromatin remodeling. The role of leo1 in vertebrate embryogenesis has not previously been examined. Here, we report that zebrafish leo1 encodes a nuclear protein that has a similar molecular structure to Leo1 proteins from other species. From a genetic screen, we identified a zebrafish mutant defective in the leo1 gene. The truncated Leo1LA1186 protein lacks a nuclear localization signal and is distributed mostly in the cytoplasm. Phenotypic analysis showed that while the initial patterning of the primitive heart tube is not affected in leo1LA1186 mutant embryos, the differentiation of cardiomyocytes at the atrioventricular boundary is aberrant, suggesting a requirement for Leo1 in cardiac differentiation. In addition, the expression levels of markers for neural crest-derived cells such as crestin, gch2, dct and mitfa, are greatly reduced in leo1LA1186 mutants, indicating a requirement for Leo1 in maintaining the neural crest population. Consistent with this finding, melanocyte and xanthophore populations are severely reduced, craniofacial cartilage is barely detectable, and mbp-positive glial cells are absent in leo1LA1186 mutants after three days of development. Taken together, these results provide the first genetic evidence of the requirement for Leo1 in the development of the heart and neural crest cell populations.
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影响因子：
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作者：
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