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The asymmetrical orientation of the lashes in the right-left organizer of the zebra fish

High resolution mapping of cilia in multidimension

Chiral Cilia Orientation in the Left-Right Organizer.

Ferreira RR(1), Pakula G(2), Klaeyle L(1), Fukui H(1), Vilfan A(3), Supatto W(2), Vermot J(4).

Cell Rep Nov. 20, 2018


Nov. 20, 2018

Chirality is a property of asymmetry between an object and its mirror image; the etymology of the word "chiral", meaning "hand" in ancient Greek, refers to the fact that the right hand and the left hand, although images of each other in symmetry with respect to a plane, are not superposable. Most molecules, many types of cells and also drugs have this asymmetry of which some of their properties depend. Julien Vermot's team at the IGBMC (CNRS/Inserm/University of Strasbourg) with the help of the group of Willy Supatto (Ecole Polytechnique, Paris) and Andrej Vilfan (Max Planck Insitute, Göttingen) used advanced live imaging techniques to show that the cilia on the surface of the cells of the right-left organizer of the zebrafish have a chiral orientation between the right and left sides. This work shows that tissues, like molecules and cells, have chiral properties and could help to understand how axes of symmetry are broken during organ genesis. Results published in the journal Cell reports on November 20, 2018.

 

The asymmetric distribution of organs within the body cavity such as the heart is established very early in embryogenesis. Symmetry breaking occurs in the so called left-right organizer, where cells are dictated where left and right embryonic sides are. Left-right symmetry breaking requires motile organelles protruding from the cell surface called cilia. It is now well established that cilia generate a directional flow in the left-right organizer that breaks the embryonic symmetry by acting as propellers. However, many observations have suggested that the chirality of proteins or cells could participate in breaking the embryonic axis of symmetry. Using intravital imaging tools based on multiphoton microscopy and dedicated image analysis approaches, the researchers had the surprise to observe that the spatial orientation of cilia and show that they are oriented asymmetrically. 

 

Considering that such asymmetry was never observed before, the researchers seeked to establish the origin of this chirality. They focused on a well-known property of cells: the planar polarity. The planar cell polarity is thought to act as a cellular compass allowing the cells to orient themselves in the planar axis of the tissues. Without it, the heart, lungs, skin and other organs would not develop properly. The researchers observed that the orientation of the cilia became symmetrical when the polarity of the cells was defective. The researchers concluded that the cellular polarity is essential to establish chirality.

 

While the planar polarity is partly responsible for the asymmetric orientation of lashes, it does not fully explain the mechanism by which cilia orient themselves asymmetrically. The researchers assume that other factors need to be taken into account: the asymmetric structure of the lash could affect their positioning as they beat, and the anchoring of the cilia and its alignment in the cell could also be involved.

 

By revealing these unexpected properties of asymmetric tissue organization, this work opens new perspectives on understanding the role of chirality on the shape and positioning of our organs.

 

This study was funded by the ANR, FRM, the EMBO Young Investigator Program, ERC and the Slovenian Research Agency.

 

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