纤毛的功能是钙介导的机械传感器,指示左右不对称,这一成果由美国哈佛医学院Shiaulou Yuan研究团队经过不懈努力而取得。相关论文发表在2023年1月6日出版的《科学》杂志上。
该研究团队证明了不动的LRO纤毛是剪切力的机械传感器,该方法结合了光镊子、光片显微镜和深度学习,可以在斑马鱼中进行体内分析。对不动的LRO纤毛的机械操作激活了纤毛内的钙瞬态,这需要阳离子通道Polycystin-2。
此外,对LRO纤毛施加机械力足以挽救和逆转缺乏活动纤毛的斑马鱼的心脏。因此,LRO纤毛是机械敏感的细胞杠杆,将生物力学力转换为钙信号,指导左右不对称。
研究人员表示,在大多数脊椎动物中,双侧对称的打破严重依赖于胚胎左右组织者(LRO)的运动纤毛,它产生定向流体流动。然而,目前还不清楚这种流动是如何被感知的。
附:英文原文
Title: Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry
Author: Lydia Djenoune, Mohammed Mahamdeh, Thai V. Truong, Christopher T. Nguyen, Scott E. Fraser, Martina Brueckner, Jonathon Howard, Shiaulou Yuan
Issue&Volume: 2023-01-06
Abstract: The breaking of bilateral symmetry in most vertebrates is critically dependent upon the motile cilia of the embryonic left-right organizer (LRO), which generate a directional fluid flow; however, it remains unclear how this flow is sensed. Here, we demonstrated that immotile LRO cilia are mechanosensors for shear force using a methodological pipeline that combines optical tweezers, light sheet microscopy, and deep learning to permit in vivo analyses in zebrafish. Mechanical manipulation of immotile LRO cilia activated intraciliary calcium transients that required the cation channel Polycystin-2. Furthermore, mechanical force applied to LRO cilia was sufficient to rescue and reverse cardiac situs in zebrafish that lack motile cilia. Thus, LRO cilia are mechanosensitive cellular levers that convert biomechanical forces into calcium signals to instruct left-right asymmetry.
DOI: abq7317
Source: https://www.science.org/doi/10.1126/science.abq7317