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Differentiating left from right in embryos: physics and biology approaches team-up to address mechanism of symmetry breaking in zebrafish

High resolution mapping of cilia in multidimension - © R. Ferreira

Physical limits of flow sensing in the left-right organizer.

Ferreira RR(1), Vilfan A(2), Julicher F(3), Supatto W(4), Vermot J(1).

Elife June 14, 2017


June 14, 2017

The asymmetrical positioning of internal organs, such as the heart, is established very early during embryogenesis and is crucial for a proper physiological activity of the internal body cavity in vertebrates. Using tools borrowed from physics and mathematics, the team of Julien Vermot at the IGBMC has shown that chemical molecules transported by the fluid flow generated by the beating of cilia are likely to promote the establishment of the left-right asymmetry in zebrafish. The results of this study were published in eLife on June 14, 2017.

 

Many studies have already shown that the establishment of left-right asymmetry depends on the fluid flow generated by the movement of cilia present in a transient structure of the embryo, called the left-right organizer. But how cells perceive this flow is still unclear. On the basis of mathematical modeling, the team of Julien Vermot tested two hypotheses to explain this sensing: either the cells of the left-right organizer detect the mechanical forces generated by the flow, or the cells perceive chemical molecules transported by the flow.

 

High resolution mapping of cilia in multidimension

To investigate this mechanism, the researchers observed the zebrafish, a transparent model organism. This feature allowed scientists to monitor the distribution of cilia in the left-right organizer at very high resolution. In collaboration with a team of imaging experts from the Ecole Polytechnique (Palaiseau), it was possible to perform an extremely precise mapping of this structure.

 

In collaboration with specialists in fluid mechanics from the Stefan Institute (Ljubljana, Slovenia) and the Max-Planck Institute (Dresden, Germany), the team of Julien Vermot was able to precisely model and quantify the microscopic flows generated by the cilia. They have shown the forces associated with the flow were weak and variable from one embryo to the next, even though all embryos had a normal establishment of the left-right asymmetry. This observation supported the hypothesis that it is unlikely the left-right asymmetry is induced by mechanical detection of the flow.

 

The researchers then mathematically simulated the diffusion of chemical molecules. Their results showed that if those molecules have a particular size and diffuse from a specific place in the left-right organizer, the establishment of the left-right asymmetry could robustly occur.

 

In the future, researchers will try to determine the nature of these chemical molecules!

 

The study was financed by the National Research Agency (ANR).

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