张力异质性指导心肌壁的形状和命运
Rashmi Priya1,2, Srinivas Allanki3, Alessandra Gentile3
1Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. rashmi.priya@crick.ac.uk.
Nature
|November 19, 2020
概括
发育中的心脏局部紧张差异决定了细胞命运的选择. 细胞拥挤会引起紧张,促使细胞形成新层,确保正确的器官发育.
科学领域:
- 发育生物学
- 细胞力学
- 机体生成
背景情况:
- 对于心脏发育至关重要,形成不同的紧和状层.
- 导致心肌病和胚胎死亡.
- 组织对称性被打破以指定状心肌细胞的机制是未知的.
研究的目的:
- 研究如何组织规模的力量和细胞机制影响细胞命运决策在心脏形.
- 阐明局部紧张异质性在特白细胞心肌细胞的特异性中的作用.
- 了解机械力量与器官模式中的信号通路之间的相互作用.
主要方法:
- 用斑马鱼作为研究心脏发育的模型生物.
- 研究了细胞拥挤和actomyosin收缩对心肌细胞分层的影响.
- 在缺陷斑马鱼模型中使用遗传马赛克.
- 使用Notch报告员表达式评估心肌细胞命运规范.
主要成果:
- 由增殖诱导的细胞拥挤驱动的局部紧张异质性决定了心肌细胞分层和状层的播种.
- 增加细胞拥挤增强了分层,而减少了这一过程.
- 即使没有像Nrg-Erbb2或血液流动这样的上游信号,诱导actomyosin可以挽救分层并促进心肌细胞命运的规范.
- 切口信号作用限制过度分层,保持心肌壁结构.
结论:
- 组织规模的力量汇聚在局部细胞力学上以产生复杂的器官形式和调节心脏轨道运动期间的细胞命运选择.
- 机械力量和信号通路之间的多层次调节相互作用确保了强大的,自我组织的器官模式.
- 了解这些机制可以帮助预防先天性心脏缺陷.
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