Fluid Dynamic Mechanism Responsible for Breaking the Left-Right Symmetry of the Human Body: The Nodal Flow

Nobutaka Hirokawa; Yasushi Okada; Yosuke Tanaka

doi:10.1146/annurev.fluid.010908.165141

Annual Review of Fluid Mechanics

Volume 41, 2009

Review Article

Fluid Dynamic Mechanism Responsible for Breaking the Left-Right Symmetry of the Human Body: The Nodal Flow

Nobutaka Hirokawa¹, Yasushi Okada¹, and Yosuke Tanaka¹
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Affiliations: Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; email: [email protected]
Vol. 41:53-72 (Volume publication date January 2009) https://doi.org/10.1146/annurev.fluid.010908.165141
© Annual Reviews

Abstract

A left-right (LR) asymmetric body plan is crucial for the development of the human body. The past decade has seen rapid progress in our understanding of the LR symmetry-breaking process in vertebrate development. A series of experimental studies has demonstrated that leftward movement of fluid at the ventral node, designated nodal flow, is the central process in symmetry breaking. Nodal flow is autonomously generated by the posteriorly tilted rotation of cilia. The underlying fluid dynamic mechanism, especially the importance of viscous interactions between the cilia and the cell surface, has been clarified by theoretical analyses. Recent experiments have suggested how this leftward nodal flow can be interpreted to create LR asymmetry. Specifically, leftward transport of lipoprotein particles, called nodal vesicular parcels (NVPs), was uncovered. Nodal flow thus triggers left-specific signaling pathways by transporting signaling molecules to the left side using NVPs.

Keyword(s): body-axis determination, cilia, kinesin, morphogen, morphogenesis, nodal vesicular parcel

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2009-01-21

2025-05-15

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Fluid Dynamic Mechanism Responsible for Breaking the Left-Right Symmetry of the Human Body: The Nodal Flow

Annual Review of Fluid Mechanics 41, 53 (2009); https://doi.org/10.1146/annurev.fluid.010908.165141

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Supplementary Data

Supplemental Movie 1: Leftward nodal flow. Nodal flow was visualized by adding fluorescent beads to the medium surrounding the ventral node of a mouse embryo at the early somite stage. 4× time lapse. Download movie file (MOV)

Supplemental Movie 2: Rotatory movement of nodal cilia. A movie sequence corresponding to Figures 6a and 6b. Download movie file (GIF)

Supplemental Movie 3: Posteriorly-tilted rotation of nodal cilia. Nodal cilia were observed by high-speed video microscopy (500 frames/s). The focus was adjusted to approximately 3 µm above the surface of the ventral node. The images of the cilia thus blur when they are near the floor and become clear when they come up to the focal plane. Note that the particle (highlighted by a red circle) does not go down to the surface but eventually goes toward the left side of the node due to the movement of the cilia. Reproduced from Okada et al. (2005) with permission. Download movie file (MOV)

Supplemental Movie 4: Rapid leftward flow and slow counterflow in a mouse nodal pit. The focal plane is first adjusted to 4 µm above the floor of the nodal pit of the mouse (bottom), where the fluid flows rapidly to the left. The focal plane is then lifted by 6 µm (middle), where circulation of the fluid is evident. Beads flow upward near the right edge and go down near the left edge. Beads above the focal plane move toward the right, while beads below the focal plane move toward the left. Finally, the focal plane is lifted twice by 6 µm (top), where the slower rightward return flow is evident. Reproduced from Okada et al. (2005) with permission. Download movie file (MOV)

Supplemental Movie 5: Leftward flow of NVPs. A ventral view of a mouse embryo whose membrane lipids have been fluorescently labeled with a DiI dye is shown. The anterior side of the node (triangular blank structure in the center) is placed upward in the movie, so that the leftward flow of NVPs appears as rightward movement in the movie. Bar, 10 µm. 20x time lapse. Reproduced from Tanaka et al. (2005). Download movie file (MOV)

Supplemental Movie 6: Release of NVPs from dynamically protruding microvilli. Detailed time-lapse observations of DiI-labeled NVPs reveal a unique ball-throwing mechanism for the release of NVPs from the tips of microvilli. Bar, 1 µm. 10x time lapse. Reproduced from Tanaka et al. (2005) with permission. Download movie file (MOV)

Supplemental Movie 7: Fragmentation of an NVP on left nodal crown cells. An NVP of approximately 0.5 µm in diameter is approaching the left wall. When it comes within 1-2 µm of the wall, it suddenly expands to twice its size and bursts into several submicron pieces that spread out along the left wall. These pieces are most likely crushed by rotating cilia. Bar, 1 µm. 16x time lapse. Reproduced from Tanaka et al. (2005) with permission. Download movie file (MOV)

Supplemental Movie 8: Animated model of NVP flow. An animated model summarizing the mechanisms of the release, transport and turnover of an NVP is shown. Copyright by Biohistory Research Hall/TokyoCinema Inc. (2005). Download movie file (MOV)