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

Takanobu A. Katoh; Toshihiro Omori; Katsutoshi Mizuno; Xiaorei Sai; Katsura Minegishi; Yayoi Ikawa; Hiromi Nishimura; Takeshi Itabashi; Eriko Kajikawa; Sylvain Hiver; Atsuko H. Iwane; Takuji Ishikawa; Yasushi Okada; Takayuki Nishizaka; Hiroshi Hamada

doi:10.1126/science.abq8148

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

Takanobu A. Katoh, Toshihiro Omori, Katsutoshi Mizuno, Xiaorei Sai, Katsura Minegishi, Yayoi Ikawa, Hiromi Nishimura, Takeshi Itabashi, Eriko Kajikawa, Sylvain Hiver, Atsuko H. Iwane, Takuji Ishikawa, Yasushi Okada, Takayuki Nishizaka, Hiroshi Hamada

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	66-71
Number of pages	6
Journal	Science
Volume	379
Issue number	6627
DOIs	https://doi.org/10.1126/science.abq8148
Publication status	Published - 2023 Jan 6

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title = "Immotile cilia mechanically sense the direction of fluid flow for left-right determination",

abstract = "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.",

author = "Katoh, {Takanobu A.} and Toshihiro Omori and Katsutoshi Mizuno and Xiaorei Sai and Katsura Minegishi and Yayoi Ikawa and Hiromi Nishimura and Takeshi Itabashi and Eriko Kajikawa and Sylvain Hiver and Iwane, {Atsuko H.} and Takuji Ishikawa and Yasushi Okada and Takayuki Nishizaka and Hiroshi Hamada",

year = "2023",

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doi = "10.1126/science.abq8148",

language = "English",

volume = "379",

pages = "66--71",

journal = "Science",

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TY - JOUR

T1 - Immotile cilia mechanically sense the direction of fluid flow for left-right determination

AU - Katoh, Takanobu A.

AU - Omori, Toshihiro

AU - Mizuno, Katsutoshi

AU - Sai, Xiaorei

AU - Minegishi, Katsura

AU - Ikawa, Yayoi

AU - Nishimura, Hiromi

AU - Itabashi, Takeshi

AU - Kajikawa, Eriko

AU - Hiver, Sylvain

AU - Iwane, Atsuko H.

AU - Ishikawa, Takuji

AU - Okada, Yasushi

AU - Nishizaka, Takayuki

AU - Hamada, Hiroshi

PY - 2023/1/6

Y1 - 2023/1/6

N2 - 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.

AB - 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.

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DO - 10.1126/science.abq8148

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SP - 66

EP - 71

JO - Science

JF - Science

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ER -

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

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