The science of having your heart in the right place

At the start of an embryo¡¯s development, cells move around in much the same way that cancer cells move later in life. From the moment the sperm fertilizes the egg, their DNA codes work to produce proteins. These in turn reproduce the cells that gather in what appears to be a formless mass. Gradually, however, a series of biochemical signals move the cells around until they begin to resemble a human being.

When this process is completed, the cells lose their capacity to move and focus instead on growth and development.

The heart¡¯s position, with the lower end pointing left, is key to connecting with veins and arteries

When embryogenesis begins, our organs are arranged in the center of the body and, among certain invertebrates, that is where they will stay. But in vertebrates such as humans, a more complex system of distribution is carried out, moving the liver to the right, for example, and the heart to the left.

In the case of the heart, once it has started to form it attracts cells from both the left and right, yet it shifts left. According to ?ngela Nieto, head of the IN research team, the accepted explanation for this asymmetrical result is that the series of signals causing the movement were repressed on the right side. Nieto¡¯s team, however, detected an additional mechanism at play. ¡°There was greater gene expression on the right side¡± ¨C triggering a larger flow of cells from the right, pushing the heart left.

Nieto and her team began by studying the process in chicken embryos. Later, they confirmed their findings in zebrafish and mice, allowing them to conclude that the mechanism worked in various species and probably in humans. ¡°The zebrafish is transparent, so cell movement is easier to study,¡± says Oscar Oca?a, who began the research 25 years ago. ¡°We demonstrated that if you arrest the function of those genes and thus the flow of cells towards the heart, the heart remains in the center in all three species.¡±

¡°The location of our organs is connected to efficient collaboration with other systems, such as the vascular system,¡± says Nieto.

The heart¡¯s position, with the lower end pointing left, is key to its connection with veins and arteries. In evolutionary terms, natural selection has favored mutations that lead to more efficient organs. That said, a human¡¯s heart is very different to an invertebrate¡¯s.

Unfortunately, the infinite number of biochemical signals that position the organs don¡¯t always work perfectly. In many cases, they are destroyed by the embryo¡¯s own security system when it detects what it thinks are errors. In some cases, development continues despite this. At birth, not only are 50% of defects heart-related, but many are linked to the heart¡¯s location.

?ngela?Nieto and her team could help our understanding of illnesses such as cancer

Nieto and her team¡¯s bid to better understand the signal system that governs embryonic development could help our understanding of illnesses such as cancer. ¡°We pinpoint the proteins that give the cells their capacity to move around,¡± says Nieto. ¡°We have been able to study this at various stages in the embryo¡¯s development and have observed how ¡®the program¡¯ comes to an end when the process is finished, but we know that it can start up again further down the line in a pathological manner.¡±

Cancer cells have recovered this capacity to move and are able to spread from the main tumor to other organs.

The Spanish team is now working on understanding the location of other organs, such as the liver, with the final goal of working out the cellular choreography that creates human beings and, at times, destroys them.

English version by Heather Galloway.?