Immotile cilia mechanically sense the direction of fluid flow for left-right determination

• 成果类型: Article
• 署名作者: Katoh, Takanobu A.; Omori, Toshihiro; Mizuno, Katsutoshi; Sai, Xiaorei; Minegishi, Katsura; Ikawa, Yayoi; Nishimura, Hiromi; Itabashi, Takeshi; Kajikawa, Eriko; Hiver, Sylvain; Iwane, Atsuko H.; Ishikawa, Takuji; Okada, Yasushi; Nishizaka, Takayuki; Hamada, Hiroshi
• 署名单位: RIKEN; Gakushuin University; Tohoku University; RIKEN; RIKEN; University of Tokyo; University of Tokyo; University of Fukui; National Center for Neurology & Psychiatry - Japan
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12763
• DOI: 10.1126/science.abq8148
• 发表日期: 2023-01-06
• 页码: 66-+
• 关键词: left-right asymmetry; left-right axis; node; mouse

摘要

Immotile cilia at the ventral node of mouse embryos are required for sensing leftward fluid flow that breaks left-right symmetry of the body. However, the flow-sensing mechanism has long remained elusive. In this work, we show that immotile cilia at the node undergo asymmetric deformation along the dorsoventral axis in response to the flow. Application of mechanical stimuli to immotile cilia by optical tweezers induced calcium ion transients and degradation of Dand5 messenger RNA (mRNA) in the targeted cells. The Pkd2 channel protein was preferentially localized to the dorsal side of immotile cilia, and calcium ion transients were preferentially induced by mechanical stimuli directed toward the ventral side. Our results uncover the biophysical mechanism by which immotile cilia at the node sense the direction of fluid flow.