Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination |
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Authors: | Okada Yasushi Takeda Sen Tanaka Yosuke Izpisúa Belmonte Juan-Carlos Hirokawa Nobutaka |
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Affiliation: | Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan. |
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Abstract: | 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. |
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