Embryonic Cells Fight to the Death in Competition to Become Part of the Organism

It's a battle to the death for embryonic cells in the early stages of mammalian development, and only the strongest will survive, according to Spanish researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) who have found that through this battle, the less active of these cells are eliminated by their stronger sisters.

This phenomenon, termed cell competition, occurs in a defined time window, between days three and seven in the development of mice.

During this period, all embryonic cells compete with each other, as explained by Dr. Cristina Claveria, first author of the study, and Dr. Miguel Torres, director of this work and head of the Department of Cardiovascular Development and Repair at CNIC.

"Thanks to cell competition, the developing organism optimizes itself by selecting the cells theoretically more capable of supporting vital functions throughout the life of the new individual," Claveria said in a press release.

According to the authors, this process is particularly key for long-lived organisms, such as humans, in which the functionality of their tissues must be maintained for an extended period of time.

Torres further explains that when cell competition is prevented, cells that normally would have lost the battle go on to contribute to the organism.

"We think, however, that this organism will probably be less capable than the one which would have been formed under normal circumstances," he said.

As it turns out, the researchers are able to determine in advance which cells will win this battle based on their levels of Myc protein, an important controller of cell metabolic capacity. Those with more of it survived, while those with less consistently lost. In addition, using a new technique developed for the production of genetic mosaics, they are capable of manipulating cells' level of the protein and, in doing so, alter the outcome of the fight.

The new study shows that the early embryo is a smorgasbord of cells with varying levels of Myc - that is, until those with higher levels eliminate those found lacking.

However, the scientists caution, it is important to understand that even those that don't make it are viable cells.

"Their removal occurs only because the embryo has more suitable cells able to replace them, and therefore this is an optimization mechanism, not a repair one," they explained.

Furthermore, the study illustrates in detail the efficiency of this process: dying loser cells are engulfed and digested by their winning neighbors, who then recycle and use all the nutrients for the benefit of the embryo.

Ultimately, this research provides answers to some of the questions raised nearly 40 years ago by Spanish scientists Ginés Morata and Pedro Ripoll, who discovered cell competition in the fruit fly as early as 1975.

Since then, the phenomenon has been suggested as a likely contributor to multiple processes, including tumor growth and tissue regeneration. Not until this study, however, was a natural function for it described.

Going forward, the scientists report that they look forward to learning more about what exactly is affected in an organism when this battle is prevented and the weaker cells are allowed to stay.

"In what sense will it be less adequate is a matter of great interest that we will address in the coming years," Torres said.