Scientists have accidentally created a mouse embryo with six legs and no genitals – revealing how changes to DNA can have major impacts on development.
The team, from the Gulbenkian Science Institute in Oeiras, Portugal, were investigating how a particular protein works during the middle stages of embryo growth.
Embryos begin as just a bundle of identical cells. As they develop, cells specialise and begin to form different body parts, generally starting at the head and moving back towards the tail – yes, even humans have tails in the early days, but it disappears around eight weeks.
Scientists already knew that, in most four-limbed mammals, both the external genitalia (the penis or clitoris) and the hind limbs develop from the same early structures.
The team, led by developmental biologist Moisés Mallo, focused on one particular receptor protein, Tgfbr1.
The protein, officially called transforming growth factor beta receptor I, is involved in the expression of genes – basically, helping decide which ones to activate where, deciding what each cell should become, for example, a blood cell, muscle tissue or a nerve cell.
In this study, researchers inactivated Tgfbr1 in mouse embryos roughly halfway through development to see how it affected development of the spinal cord.
What they found was an embryo that developed extra limbs instead of genitals, with a number of organs growing outside of its body.
It seems that, without this protein, other genes kicked into action, telling the cells to grow into legs rather than genitals.
It wasn’t quite what the team was expecting.
However, they now hope further research will enable them to determine whether Tgfbr1, and its relatives, can affect DNA in other systems – such as metastatic cancer.
Writing in the journal Nature Communications, they said: ‘Identification [the] mechanisms and determining whether they also operate in other physiological and pathological processes under the control of members of the [Tgfbr1] family might have far reaching implications for our understanding of morphogenetic processes and disease.’
Existing cancer treatments already target tumours’ DNA, meaning better understanding of how they work could help create new and better options.
They are also investigating whether the protein is also behind the mysterious hemipenis, a forked double penis seen in some snakes.
