Molecular genetic analysis of relationship between traveling wave and constant wave of molecular clock in somitogenesis

体节发生分子钟行波与恒定波关系的分子遗传学分析

• 批准号: 17570186
• 负责人: TAKAHASHI Yu
• 金额: $ 2.24万
• 依托单位: National Institute of Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17570186/
• 关键词: Developmental biology; Genetics; Mouse; Pattern formation; Notch signaling; 分子時計

Mesp1 and Mesp2 are homologous transcription factors that are co-expressed in the anterior presomitic mesoderm (PSM) during mouse somitogenesis. The loss of Mesp2 alone in our conventional Mesp2-null mice results in the complete disruption of somitogenesis, including segment border formation, rostro-caudal patterning and epithelialization of somitic mesoderm. This has led us to interpret that Mesp2 is solely responsible for somitogenesis. Our novel Mesp2 knock-in alleles, however, exhibit a remarkable upregulation of Mesp1. Removal of the pgk-neo cassette from the new allele leads to localization of Mesp1 and several gene expression, and somite formation in the tail region. Moreover, a reduction in the gene dosage of Mesp1 by one copy disrupts somite formation, confirming the involvement of Mesp1 in the rescue events. Furthermore, we find that activated Notch1 knock-in significantly upregulates Mesp1 expression, even in the absence of a Notch signal mediator, Psen1. This indicates that the Psen1-independent effects of activated Notch1 are mostly attributable to the induction of Mesp1. However, we have also confirmed that Mesp2 enhances the expression of the Notch1 receptor in the anterior PSM. The activation and subsequent suppression of Notch signaling might thus be a crucial event for both stripe pattern formation and boundary formation.

Mesp 1和Mesp 2是同源转录因子，在小鼠体节发生过程中在前体前中胚层（PSM）共表达。在我们的常规Mesp 2-null小鼠中，Mesp 2单独的损失导致体节发生的完全破坏，包括节段边界形成、喙尾图案化和体节中胚层的上皮化。这使我们解释说，Mesp 2是唯一负责体节发生。然而，我们新的Mesp 2基因敲入等位基因表现出Mesp 1的显著上调。从新等位基因中去除pgk-neo盒导致Mesp 1和几个基因表达的定位，以及尾区的体节形成。此外，Mesp 1基因剂量减少一个拷贝会破坏体节的形成，证实了Mesp 1参与了拯救事件。此外，我们发现，激活Notch 1敲入显着上调Mesp 1的表达，即使在没有Notch信号介导，Psen 1。这表明激活的Notch 1的Psen 1非依赖性效应主要归因于Mesp 1的诱导。然而，我们也证实了Mesp 2增强了前PSM中Notch 1受体的表达。因此，Notch信号的激活和随后的抑制可能是条纹图案形成和边界形成的关键事件。

项目成果

Transcription factors Mesp2 and Paraxis have critical roles in axial muscuioskeletal formation

转录因子 Mesp2 和 Paraaxis 在轴向肌肉骨骼形成中发挥关键作用

• 发表时间: 2007
• 期刊: Developmental Dynamics (in press)
• 作者: 高橋雄;高木篤也;平岡秀一;古関明彦;菅野純;Alan Rawls;相賀裕美子
• 通讯作者: 相賀裕美子

Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation.

转录因子 Mesp2 和 Paraaxis 在轴向肌肉骨骼形成中发挥着关键作用。

• 发表时间: 2007
• 期刊: Developmental Dynamics 236
• 作者: 高橋雄;高木篤也;平岡秀一;他4名
• 通讯作者: 他4名

Appropriate suppression of Notch signaling by Mesp factors is essential for stripe pattern formation leading to segment boundary formation.

Mesp 因子对 Notch 信号传导的适当抑制对于导致片段边界形成的条纹图案形成至关重要。

• 发表时间: 2007
• 期刊: Dev. Biol. 304
• 作者: Takahashi Y;Yasuhiko Y;Kitajima S;Kannno;J;Saga Y
• 通讯作者: Saga Y

The Mesp2 transcription factor establishes segmental borders by suppressing Notch activity

• DOI: 10.1038/nature03591
• 发表时间: 2005-05-19
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Morimoto, M;Takahashi, Y;Saga, Y
• 通讯作者: Saga, Y