The regulation of cell differentiation and morphogenesis on mamalian early development

细胞分化和形态发生对哺乳动物早期发育的调控

• 批准号: 08408033
• 负责人: HAMADA Hiroshi
• 金额: $ 18.69万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08408033/
• 关键词: Left-right asymmetry; Lefty; transcriptional regulation

Both lefty-1 and lefty-2 genes are expressed on the left side of developing mouse embryos and are implicated in left-right (L-R) axis formation. With the use of transgenic analysis, the transcriptional regulatory regions of these genes responsible for their L-R asymmetric expression have now been investigated. The 9.5-kb upstream region of lefty-1 and the 5.5-kb upstream region of lefty-2 reproduced the expression pattern of the corresponding gene. Examination of deletion constructs revealed the presence of a left side-specific enhancer (ASE) that is essential and sufficient for lefty-2 asymmetric expression. In contrast, the asymmetric expression of lefty-1 was shown to be determined by a combination of bilateral enhancers and a right side-specific silencer (RSS). The 9.5-kb region of lefty-1 and the 5.5-kb region of lefty-2 responded to iv and inv, upstream genes of lefty-1 and lefty-2. The regulation of lefty-2 by iv and inv was mediated by ASE. These results suggest that, in spite of the similarities between lefty-1 and lefty-2, different regulatory mechanisms underlie their asymmetric expression.

lefty-1和lefty-2基因都在发育中的小鼠胚胎的左侧表达，并与左右（L-R）轴的形成有关。随着转基因分析的使用，这些基因的转录调控区负责他们的L-R不对称表达现在已经调查。lefty-1的9.5kb上游区和lefty-2的5.5kb上游区再现了相应基因的表达模式。缺失结构的检查揭示了左侧特异性增强子（ASE）的存在，这是必需的和足够的lefty-2不对称表达。相反，leftty-1的不对称表达被证明是由双侧增强子和右侧特异性沉默子（RSS）的组合决定的。lefty-1和lefty-2的9.5kb区域分别与lefty-1和lefty-2的上游基因iv和inv反应。iv和inv对lefty-2的调节作用均由ASE介导。这些结果表明，尽管左撇子-1和左撇子-2之间的相似性，不同的调控机制的基础上，他们的不对称表达。

项目成果

Meno,C.: "Left-right asymmetric expression of the TGF-family member lefty in mouse embryo" Nature. 381. 151-155 (1996)

Meno,C.：“TGF-家族成员左撇子在小鼠胚胎中的左右不对称表达”自然。

Hirose,K.: "cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor (Arnt2) with close sequencesimilarity to the aryl hydrocarbon receptor nuclear translocator (Arnt)" Mol.Cell.Biol.16. 1706-1713 (1996)

Hirose,K.：“新型碱性螺旋-环-螺旋/PAS 因子 (Arnt2) 的 cDNA 克隆和组织特异性表达，与芳基烃受体核易位子 (Arnt) 具有密切的序列相似性”Mol.Cell.Biol.16。

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Meno,C.,: "Left-right asymmetric expression of unique TGF β-related gene lefty in mouse embryo" Nature. 381. 151-155 (1996)

Meno, C.,：“小鼠胚胎中独特的 TGF β 相关基因的左右不对称表达”，《自然》，381. 151-155 (1996)。

Saijho,Y.,: "Identification of putative downstream genes of Oct-3,a pluripotent cell-specific transcription factor." Genes to Cells. 1. 239-252 (1996)

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