Ancient viral DNA plays role in early embryo development

Viral genetic material, integrated into our DNA millions of years ago, has an essential role in a key early stage in embryo development.

Using a mouse model, scientists in Spain have shown that endogenous retroviruses, part of the genome that was incorporated into DNA following ancient viral infection, influences one of the very first steps in early development. One of these endogenous retroviruses encodes a specific protein shown to control the switch from totipotency to pluripotency, a step that is required for the mouse embryo to progress past the two-cell stage of development.

'It is a totally new role for endogenous retroviruses' senior author Dr Nabil Djouder from the Spanish National Cancer Research Centre (CNIO), Madrid said. 'We discovered a new mechanism that explains how an endogenous retrovirus directly controls pluripotency factors'.

Totipotent stem cells can form all the cell types in an organism, plus extraembryonic tissues, such as the placenta. Embryonic cells within the first couple of cell divisions after fertilisation are the only cells that are totipotent and have the potential to divide until they create a whole organism. Pluripotent stem cells can form most, or all, cell types in an organism, but cannot develop into a whole organism on their own as they are unable to organise into an embryo.

The timing of the switch from embryonic cells being totipotent to pluripotent is important for ensuring the embryo has sufficient time to adjust, and therefore is tightly controlled. Researchers at CNIO have described, in Science Advances, one potential mechanism that regulates the timing of this transition.

They have shown that high expression of one retroviral protein during the totipotency stage blocks the binding of a mouse protein to its active sites, which stops the transition to pluripotecy. This is at the point where the embryo is made up of only two cells. As the expression of the retroviral protein gradually decreases, the mouse protein can bind to its sites, activating the switch to pluripotency and allowing the embryo to further divide and develop.

These experiments have been carried out in mice, so a similar mechanism in human development would need to be confirmed. However, it is known that at least eight percent of the human genome is derived from viruses.

These findings will add to the understanding of the key switches in early development, with implications for embryo modelling and developmental biology research. In particular, it could provide a way to control totipotency, which is important for generating stable cell lines that can be used in a wide range of research applications, from cancer research to regenerative medicine.

Dr Marta Shahbazi, a researcher at the MRC Laboratory of Molecular Biology in Cambridge, who was not involved in the research, explained that: 'In order to use these cells in regeneration and embryonic modelling, the next step would be to demonstrate whether these cells have greater potential, and to develop methods so that they can mimic the early stages of development.'