Mechanism of somite segmentation by bHLH transcription factors

bHLH转录因子体节分割机制

• 批准号: 13670116
• 负责人: BESSHO Yasumasa
• 金额: $ 2.3万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670116/
• 关键词: somite; segmentation; transcription factor; bHLH; oscillation; proteasome; Ubiquitination; molecular clock; bHLH因子; ノックアウトマウス

Somites, the metameric units of vertebrate embryos, are generated by periodical segmentation, which is regulated by a molecular clock. Hes7, a bHLH gene essential for somite segmentation, displays cyclic expression in the presomitic mesoderm (PSM) with 2 h cycles synchronized with somite formation. Hes7 is also essential for the oscillatory expression of the other gene such as Lunatic fringe (Lfng). It is likely that the cyclic expression of Hes7 is involved in the molecular clock in somite segmentation. Thus, we analyzed the mechanism of the oscillatory expression of Hes7.We show that Hes7 protein is also expressed in a dynamic manner, which depends on proteasome-mediated degradation. Spatial comparison revealed that Hes7 and Lfng transcription occurs in the Hes7 protein-negative domains. Furthermore, Hes7 and Lfng transcription is constitutively up-regulated in the absence of Hes7 protein and down-regulated by stabilization of Hes7 protein. Thus, periodic repression by Hes7 protein is critical for the cyclic transcription of Hes7 and Lfng, and this negative feedback represents a molecular basis for the segmentation clock.

体节是脊椎动物胚胎的异构体单位，它是通过周期性的分割产生的，这是由分子时钟调节的。Hes7是体节形成所必需的bHLH基因，在卵裂期前的中胚层(PSM)中呈周期性表达，与体节的形成同步，周期为2小时。Hes7对于其他基因的振荡表达也是必不可少的，如Lfng。Hes7的循环表达可能参与了体节分割的分子时钟。因此，我们分析了Hes7蛋白振荡表达的机制，我们发现Hes7蛋白也以动态的方式表达，这依赖于蛋白酶体介导的降解。空间比较表明，Hes7和Lfng转录发生在Hes7蛋白阴性区域。此外，Hes7和Lfng的转录在没有Hes7蛋白的情况下结构性上调，而在Hes7蛋白稳定时下调。因此，Hes7蛋白的周期性抑制对Hes7和Lfng的循环转录至关重要，这种负反馈代表了分段时钟的分子基础。

项目成果

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