Ribosome Biogenesis Factor Bms1-like Is Essential for Liver Development in Zebrafish
Ribosome Biogenesis Factor Bms1-like Is Essential for Liver Development in Zebrafish
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核糖体生物发生因子 Bms1 对斑马鱼肝脏发育至关重要
DOI：
10.1016/j.jgg.2012.07.007
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发表时间：
2012-09-01
影响因子：
5.9
通讯作者：
Lo, Lijan
中科院分区：
文献类型：
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作者：
Wang, Yong;Luo, Yue;Lo, Lijan
核仁中核糖体的生物合成需要大量核仁蛋白和小非编码 RNA。其中包括核糖体生物发生因子Bms1，该因子从酵母到人类都高度保守。在酵母中，Bms1 通过将 Rcl1 招募到前核糖体来启动核糖体生物合成。然而，人们对 Bms1 在脊椎动物中的生物学功能知之甚少。在这里，我们报道 Bms1 在斑马鱼肝脏发育中发挥着重要作用。我们鉴定了斑马鱼 bms1l(sq163) 突变体，其 bms1 样基因 (bms1l) 中携带 T 到 A 突变。该突变导致 Bms1l 中 GTPase 基序中的 L-152 替换为 Q(152)。令人惊讶的是，bms1l(sq163) 突变导致受精后 3 天 (dpf) 后肝脏、外分泌胰腺和肠道发育不全。与bms1l sq163突变体表型一致，野生型胚胎的整体原位杂交（WISH）表明bms1l转录本在整个消化道及其附属器官中丰富。磷酸组蛋白 3 (P-H3) 免疫染色和 TUNEL 测定表明，bms1l(sq163) 导致肝脏发育不良的后果之一是肝母细胞增殖受损，而不是细胞凋亡。因此，我们的研究结果表明 Bms1l 对于斑马鱼肝脏发育是必需的。
Ribosome biogenesis in the nucleolus requires numerous nucleolar proteins and small non-coding RNAs. Among them is ribosome biogenesis factor Bms1, which is highly conserved from yeast to human. In yeast, Bms1 initiates ribosome biogenesis through recruiting Rcl1 to pre-ribosomes. However, little is known about the biological function of Bms1 in vertebrates. Here we report that Bms1 plays an essential role in zebrafish liver development. We identified a zebrafish bms1l(sq163) mutant which carries a T to A mutation in the gene bms1-like (bms1l). This mutation results in L-152 to Q(152) substitution in a GTPase motif in Bms1l. Surprisingly, bms1l(sq163) mutation confers hypoplasia specifically in the liver, exocrine pancreas and intestine after 3 days post-fertilization (dpf). Consistent with the bms1l sq163 mutant phenotypes, whole-mount in situ hybridization (WISH) on wild type embryos showed that bms1l transcripts are abundant in the entire digestive tract and its accessory organs. Immunostaining for phospho-Histone 3 (P-H3) and TUNEL assay revealed that impairment of hepatoblast proliferation rather than cell apoptosis is one of the consequences of bms1l(sq163) giving rise to an underdeveloped liver. Therefore, our findings demonstrate that Bms1l is necessary for zebrafish liver development.