Wnt/β-catenin通路调节心脏膜形成的过程
Adam F L Hurlstone1, Anna-Pavlina G Haramis, Erno Wienholds
1Netherlands Institute for Developmental Biology, Hubrecht Laboratory and Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Nature
|October 10, 2003
概括
截断的腺瘤多样性大肠杆菌 (Apc) 激活了Wnt/β-catenin信号传输,导致斑马鱼的心脏缺陷. 这一途径对于在发育过程中决定心内细胞命运至关重要.
科学领域:
- 发育生物学 发展生物学
- 分子生物学分子生物学
- 心血管生物学 心血管生物学
背景情况:
- 截断的腺瘤多样性大肠杆菌 (Apc) 构成性地激活了Wnt/β-catenin信号通路.
- Apc在胚胎发育中起着至关重要的作用,截断的Apc可以防止小鼠的胃化.
研究的目的:
- 调查截断的Apc在斑马鱼发育中的作用.
- 阐明Wnt/β-catenin信号传递对心脏发育和内心细胞命运的特定影响.
主要方法:
- 生成斑马鱼与截断的Apc.
- 分析了心脏循环,内心脏形成和β-catenin局部化.
- 使用了TCF报告员测定和评估的门标记表达.
- 检查了细胞增殖和上皮细胞-介质细胞过渡.
主要成果:
- 斑马鱼与截断的Apc完成了胃流动,但表现出心脏循环缺陷和过度的内心形成.
- 过度表达Apc或Wnt抑制剂Dkk1阻止了缓冲的形成.
- 突变心脏显示广泛的核β-catenin和TCF记者活动,与野生类型的心脏不同,它仅限于形成的细胞.
- 门标记被上调,在整个内心脏中发生了增殖/上皮层-介质酶过渡.
结论:
- 在斑马鱼中,Wnt/β-catenin信号传递对于正常的心脏发育至关重要.
- 这种途径的异常激活会通过改变内心细胞命运导致心脏形.
- 确定了Wnt/β-catenin信号传递在调节内心细胞命运和膜发育中的新型作用.
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