Mechanism of nodal flow: A conserved symmetry breaking event in left-right axis determination

Yasushi Okada, Sen Takeda, Yosuke Tanaka, Juan Carlos Izpisúa Belmonte, Nobutaka Hirokawa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

368 Scopus citations


The leftward flow in extraembryonic fluid is critical for the initial determination of the left-right axis of mouse embryos. It is unclear if this is a conserved mechanism among other vertebrates and how the directionality of the flow arises from the motion of cilia. In this paper, we show that rabbit and medakafish embryos also exhibit a leftward fluid flow in their ventral nodes. In all cases, primary monocilia present a clockwise rotational-like motion. Observations of defective ciliary dynamics in mutant mouse embryos support the idea that the posterior tilt of the cilia during rotational-like beating can explain the leftward fluid flow. Moreover, we show that this leftward flow may produce asymmetric distribution of exogenously introduced proteins, suggesting morphogen gradients as a subsequent mechanism of left-right axis determination. Finally, we experimentally and theoretically characterize under which conditions a morphogen gradient can arise from the flow.

Original languageEnglish (US)
Pages (from-to)633-644
Number of pages12
Issue number4
StatePublished - May 20 2005
Externally publishedYes

Bibliographical note

Funding Information:
We thank Masato Ohta and Kazuhiro Eto for technical advice on manipulation of mouse embryos; Hidetaka Kosako and Kenji Shimamura for technical assistance on manipulation of chick embryos; Hiroshi Hamada for the gift of the nodal probe; Atsuko Shimada, Kouichi Aizawa, Hiroshi Mitani, and Akihiro Shima for the gift of medakafish embryos; Naoto Matsuda and Masayoshi Mishina for the gift of zebrafish embryos; Shigeki Yasumasu for the hatching enzyme; Tomohiro Furukawa and Katsuyuki Abe for assistance in the design of the microscope; and Bruene Venus for AxioImager and Apotome. We also thank Daisuke Furihata, Hisashi Okamoto, Naoto Nagaosa, and Seiji Miyashita for the stimulating discussions on the hydrodynamic aspects of this phenomenon at the earliest stage of this project; Javier Buceta and Diego Rasskin-Gutman for the constructive comments on this manuscript; and Marta Ibañes for the revision, comments, and all the numerical analyses of the distribution of proteins shown in the Supplemental Data. Part of the results (posteriorly tilted rotation-like beating of cilia) of this paper was presented in the annual meetings of the Japanese Association for Anatomists in 2002 and 2003, International Meeting of the Interest Group for Cilia, Mucus and Mucociliary Interactions supported by the PCD Foundation held in Miami in 2002 and in the annual meeting of the Japan Society for Cell Biology in 2003. This work was supported by a Center of Excellence Grant-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan to N.H. and by the National Institutes of Health to J.-C.I.B.

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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