The fabulous embryonic process that places the heart on the left brought to light

Where does the left-right asymmetry of animals’ bodies come from? If embryology cannot answer the question of why, it illuminates the how. We have the heart on the left? It is, on the scale of evolutionary times, the fruit of chance and necessity, as Jacques Monod (1910-1976), Nobel Prize in medicine, so aptly recounted. But it is also, on the scale of the embryo, the outcome of a tiny and formidable cellular and molecular saga. A saga recounted by two studies of prodigious elegance, published in the journal Science of January 6.

These two studies – one conducted on zebrafish by Americans, the other on the mouse by Japanese people – unravel a tough riddle. Remarkably, they reveal, in these two species, a set of molecular constructions developed identically or almost. Thus proving that over the course of evolution the mechanism governing the lateral fate of organs has been preserved. It is therefore also probably at work in the human embryo.

Zebrafish, mouse, cow, pig, human… All these species have a triple body axis. The first two are obvious: obviously, the head differs from the tail or the feet (this is the antero-posterior axis); and the dorsal side, from the ventral side. But the third axis is more secret: the right-left asymmetry of many organs is hidden under the skull and in the entrails. In the vast majority of humans, the heart and spleen are on the left, while the liver and gallbladder are on the right. Our intestines always coil counter-clockwise; and the two hemispheres of our brain are also asymmetrical…

In one in ten thousand people, however, the heart is on the right. When all the viscera form a mirror image of their usual position, this genetic abnormality, or situs inversus, usually not a problem. In 2019, it was thus discovered, during an autopsy, that a 99-year-old woman lived normally with this anatomical particularity. “But when the inversion of the viscera is incomplete, it creates health problems”explains Maximilian Fürthauer, of the Valrose Institute of Biology, in Nice (CNRS, Inserm, Côte d’Azur University).

The “Nodal” gene

The genes that govern head-tail or back-belly asymmetries were discovered in the 1980s. “But it took until 1995 to identify a gene that is only activated on the left side of the embryo”, explains Maximilian Fürthauer. This gene, called “Nodal”, plays a key role in this matter – we will come back to this.

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