Cilia function as calcium-mediated mechanosensors that instruct left-right asymmetry

• 成果类型: Article
• 署名作者: Djenoune, Lydia; Mahamdeh, Mohammed; V. Truong, Thai; Nguyen, Christopher T.; Fraser, Scott E.; Brueckner, Martina; Howard, Jonathon; Yuan, Shiaulou
• 署名单位: Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard Medical School; Cleveland Clinic Foundation; Massachusetts Institute of Technology (MIT); Yale University; Yale University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13543
• DOI: 10.1126/science.abq7317
• 发表日期: 2023-01-06
• 页码: 71-77
• 关键词: kupffers vesicle; mouse embryo; fluid-flow; nodal flow; polycystin-2; DYNAMICS; channel; brain; cells; light

摘要

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.