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同色异体单位，是通过周期性分割产生的，受分子钟调节。 Hes7 是体节分割所必需的 bHLH 基因，在体节前中胚层 (PSM) 中显示周期性表达，2 小时周期与体节形成同步。 Hes7 对于 Lunatic fringe (Lfng) 等其他基因的振荡表达也是必需的。 Hes7 的循环表达很可能参与体节分割的分子钟。因此，我们分析了Hes7振荡表达的机制。我们发现Hes7蛋白也以动态方式表达，这取决于蛋白酶体介导的降解。空间比较显示 Hes7 和 Lfng 转录发生在 Hes7 蛋白阴性结构域中。此外，Hes7 和 Lfng 转录在 Hes7 蛋白不存在的情况下组成性上调，并通过 Hes7 蛋白的稳定化下调。因此，Hes7 蛋白的周期性抑制对于 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。