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UNSW Embryology

Week 3 Movies - Left/Right Assymetry

© Dr Mark Hill (2008)

Acknowledgements

Left/Right Assymetry

During week 3 left/right assymetry is established. Experiments in the mouse embryo show that directional rotation of cilia located at the node (Hensen's node) can lead to the movement of fluid, and any substances in that fliud in a direction at the node. This leads to assymetric distribution of secreted morphogens that can bind specifically to one side of the embryonic disc. The movie on this page is from a paper which not only shows the direction of roation of cilia, but also generates a model to explain the possible mechanism/function of this directional rotation.

Trajectory of Node Cilia Movement

Motion of Node Cilia

(20 times slower than real time) See Figure 2A for details. (320x240, 13 sec, 4.7 Mb)

From: Nonaka S, Yoshiba S, Watanabe D, Ikeuchi S, Goto T, et al. (2005) De Novo Formation of Left–Right Asymmetry by Posterior Tilt of Nodal Cilia. PLoS Biol 3(8): e268

Trajectory of Node Cilia Movement

(A) Trace of node cilia in enhanced DIC images after background subtraction. Positions of root are indicated in black, and tip in blue, green, and orange. Most cilia have a pattern consistent with the projection of a tilted cone (blue and green, see original article text) whereas some cilia move in a D-shape (orange). A, P, L, and R refer to anterior, posterior, left, and right sides of the node, respectively. The direction of cilia rotation was clockwise (arrows).

(B) Relationship between essentially rotatory movement of cilia and their projected images at various tilt angles.

From: Nonaka S, Yoshiba S, Watanabe D, Ikeuchi S, Goto T, et al. (2005) De Novo Formation of Left–Right Asymmetry by Posterior Tilt of Nodal Cilia. PLoS Biol 3(8): e268

Flow Generation Mechanism

Circular clockwise motion of a cilium can generate directional leftward flow if its axis is not perpendicular to the cell surface but tilted posteriorly. Due to distance from the cell surface, a cilium in the leftward phase (red arrow) drags surrounding water more efficiently than the rightward phase (blue arrow), resulting in leftward force in total (purple arrow). (see original article text)

The rotating cilium is drawn slightly bent due to viscous resistance, as seen in the movie above.

From: Nonaka S, Yoshiba S, Watanabe D, Ikeuchi S, Goto T, et al. (2005) De Novo Formation of Left–Right Asymmetry by Posterior Tilt of Nodal Cilia. PLoS Biol 3(8): e268

Reference

Nonaka S, Yoshiba S, Watanabe D, Ikeuchi S, Goto T, Marshall WF, Hamada H. De novo formation of left-right asymmetry by posterior tilt of nodal cilia. PLoS Biol. 2005 Aug;3(8):e268. "In the developing mouse embryo, leftward fluid flow on the ventral side of the node determines left-right (L-R) asymmetry. However, the mechanism by which the rotational movement of node cilia can generate a unidirectional flow remains hypothetical. Here we have addressed this question by motion and morphological analyses of the node cilia and by fluid dynamic model experiments. We found that the cilia stand, not perpendicular to the node surface, but tilted posteriorly. We further confirmed that such posterior tilt can produce leftward flow in model experiments. These results strongly suggest that L-R asymmetry is not the descendant of pre-existing L-R asymmetry within each cell but is generated de novo by combining three sources of spatial information: antero-posterior and dorso-ventral axes, and the chirality of ciliary movement."

PLoS: Link to PLoS Article

Citation: Nonaka S, Yoshiba S, Watanabe D, Ikeuchi S, Goto T, et al. (2005) De Novo Formation of Left–Right Asymmetry by Posterior Tilt of Nodal Cilia. PLoS Biol 3(8): e268

See also: Okada Y, Takeda S, Tanaka Y, Belmonte JC, Hirokawa N. Okada Y, Takeda S, Tanaka Y, Belmonte JC, Hirokawa N. Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination. Cell. 2005 May 20;121(4):633-44.

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