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刺-Wnt 交叉声调节小鼠下下腺形态发生
Yunhong Song1, Yamin Chen2, Qian Wang1
1School of Stomatology, Quanzhou Medical College, Quanzhou, Fujian, China.
概括
鼠标的唾液腺发育依赖于刺 (Hh) 信号. 这项研究表明,Hh通常抑制Wnt活动,抑制Wnt可以挽救由Hh通路中断引起的缺陷.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
背景情况:
- 鼠下腺 (SMG) 的发育是分支形态发生的模型.
- 索尼克 (Shh) 对早期SMG发展至关重要,但其下游效应和通路相互作用尚未完全理解.
研究的目的:
- 为了研究在SMG形态发生过程中 (Hh) 和Wnt信号之间的功能相互作用.
- 阐明Hh信号在调节Wnt活动中的作用,用于发育唾液腺.
主要方法:
- 在怀孕小鼠中使用vismodegib对Hh信号的体内药理抑制.
- 使用Hh和/或Wnt抑制剂 (vismodegib,XAV939) 的SMG体内器官培养.
- 对基因表达 (Ptch1,Gli1,Axin2,Lef1) 和蛋白质定位 (β-catenin) 的分析.
主要成果:
- Hh抑制导致SMG严重的形态缺陷,减少分支,以及无组织的管道.
- Hh抑制导致了Hh基因的下调和Wnt通路活性的上调 (增加核β-catenin,增加Axin2和Lef1表达).
- 在Hh抑制的SMG培养物中,共抑制Wnt信号部分挽救了分支缺陷.
结论:
- 刺 (Hh) 信号通过强烈抑制Wnt通路来促进小鼠SMG形态发生.
- 对于正常的唾液腺发育来说,Hh和Wnt信号之间的新型抑制交叉是必不可少的.
- 了解这种交叉声提供了关于唾液腺器官生成和潜在的治疗点的见解.
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