Absence of Radial Spokes in Mouse Node Cilia Is Required for Rotational Movement but Confers Ultrastructural Instability as a Trade-Off.
Determination of left-right asymmetry in mouse embryos is established by a leftward fluid flow that is generated by clockwise rotation of node cilia. How node cilia achieve stable unidirectional rotation has remained unknown, however. Here we show that brief exposure to the microtubule-stabilizing drug paclitaxel (Taxol) induces randomly directed rotation and changes the ultrastructure of node cilia. In vivo observations and a computer simulation revealed that a regular 9+0 arrangement of doublet microtubules is essential for stable unidirectional rotation of node cilia. The 9+2 motile cilia of the airway, which manifest planar beating, are resistant to Taxol treatment. However, the airway cilia of mice lacking the radial spoke head protein Rsph4a undergo rotational movement instead of planar beating, are prone to microtubule rearrangement, and are sensitive to Taxol. Our results suggest that the absence of radial spokes allows node cilia to rotate unidirectionally but, as a trade-off, renders them ultrastructurally fragile.
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan. Electronic address: k_shino@cc.tuat.ac.jp.
Kyosuke
K
Shinohara
Department of Biomedical Engineering, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
Duanduan
D
Chen
Research Center for Ultra-high Voltage Electron Microscopy, Osaka University, Osaka 567-0047, Japan.
Tomoki
T
Nishida
Ultrastructural Research Team, Center for Life Science Technologies, RIKEN, Kobe 650-0047, Japan.
Kazuyo
K
Misaki
Ultrastructural Research Team, Center for Life Science Technologies, RIKEN, Kobe 650-0047, Japan.
Shigenobu
S
Yonemura
Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Hiroshi
H
Hamada
D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D002923:Cilia / Q000235:genetics* / Q000502:physiology / Q000648:ultrastructure; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage
D017239:Paclitaxel