Hox genes are vital for development in nearly all animals where they oversee cell directions along the head-to-tail axis of an embryo, and tell the cells what body parts to become. Misregulation of the Hox genes can lead to developmental issues resulting in miscarriage, birth defects or cancer.
'I don't think we can understand development or disease without understanding Hox genes,' said Dr Esteban Mazzoni, from New York University, co-senior author of the article published in Science. 'Writing or building new pieces of the genome could help us to test for sufficiency – in this case, find out what the smallest unit of the genome is necessary for a cell to know where it is in the body.'
How Hox genes are regulated to switch on and off their expression has been difficult to study using genome editing because they occur in clusters, so any off-target effects are likely to compromise other Hox genes.
Using rat DNA in the mouse's genome allowed it to be easily distinguishable, due to the different species used.
The rat Hox clusters were sufficient to regulate the mouse's genes and no other elements were needed. The compact nature of Hox clusters also contained all the information for the cells to know their intended position.
In the future, the researchers hope synthetic DNA technology can be used to help understand different animals' development, as well as help treat human diseases.
'More broadly, this synthetic DNA technology, for which we have built a kind of factory, will be useful for studying diseases that are genomically complicated and now we have a method for producing much more accurate models for them,' explained Professor Jef Boeke, co-senior author.