By accidently producing a mouse embryo with six legs and no genitalia, researchers have demonstrated how significant alterations to DNA can affect development.
The group, from the Gulbenkian Science Institute in Oeiras, Portugal, was examining the function of a specific protein in the intermediate phases of embryonic development.
All that an embryo is at first is a bundle of identical cells. Cells specialize and start to produce distinct body parts as they develop; this usually starts at the head and moves back towards the tail. Yes, even humans have tails in their early stages of development, but they disappear after eight weeks.
It was previously known by scientists that the majority of four-limbed mammals grow their hind limbs and external genitalia (the penis or clitoris) from the same early tissues.
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.
