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Science 338 (6104): 226-231

Copyright © 2012 by the American Association for the Advancement of Science

Cilia at the Node of Mouse Embryos Sense Fluid Flow for Left-Right Determination via Pkd2

Satoko Yoshiba,1 Hidetaka Shiratori,1 Ivana Y. Kuo,2 Aiko Kawasumi,1,* Kyosuke Shinohara,1 Shigenori Nonaka,3 Yasuko Asai,1 Genta Sasaki,1 Jose Antonio Belo,4 Hiroshi Sasaki,5 Junichi Nakai,6 Bernd Dworniczak,7 Barbara E. Ehrlich,2 Petra Pennekamp,7,8,{dagger} Hiroshi Hamada1,{dagger}

Abstract: Unidirectional fluid flow plays an essential role in the breaking of left-right (L-R) symmetry in mouse embryos, but it has remained unclear how the flow is sensed by the embryo. We report that the Ca2+ channel Polycystin-2 (Pkd2) is required specifically in the perinodal crown cells for sensing the nodal flow. Examination of mutant forms of Pkd2 shows that the ciliary localization of Pkd2 is essential for correct L-R patterning. Whereas Kif3a mutant embryos, which lack all cilia, failed to respond to an artificial flow, restoration of primary cilia in crown cells rescued the response to the flow. Our results thus suggest that nodal flow is sensed in a manner dependent on Pkd2 by the cilia of crown cells located at the edge of the node.

1 Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST), Japan Science and Technology Corporation (JST), 1-3 Yamada-oka, Suita, 565-0871 Osaka, Japan.
2 Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA.
3 Laboratory for Spatiotemporal Regulations, National Institute for Basic Biology, Nishigonaka 38, Myodaiji, Okazaki, 444-8585 Aichi, Japan.
4 Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, and IBB-Institute for Biotechnology and Bioengineering, Universidade do Algarve, Campus de Gambelas, 8005-135 Faro, Portugal.
5 Laboratory for Embryonic Induction, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
6 Saitama University Brain Science Institute, 255 Shimo-Okubo, Sakura-ku, Saitama 338-8570, Japan.
7 Universitätsklinikum Münster, Institut für Humangenetik, Vesaliusweg 12-14, 48149 Münster, Germany.
8 Universitaetsklinikum Muenster, Klinik für Kinder- und Jugendmedizin, Allgemeine Pädiatrie, Albert-Schweitzer-Campus 1, 48149 Muenster, Germany.

* Present address: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, 980-8578 Miyagi, Japan.

{dagger} To whom correspondence should be addressed. E-mail: petra.pennekamp{at}uni-muenster.de (P.P.); hamada{at}fbs.osaka-u.ac.jp (H.H.)


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