Hox gene–specific cellular targeting using split intein Trojan exons

What is it about?

The brain is composed of hundreds of cell types. To understand what these different cell types do requires selectively monitoring and perturbing their activity. This is best accomplished using genetic methods that allow each cell type to be targeted based on the genes it expresses. Such targeting methods, however, frequently disrupt the function of the genes used to perform the targeting. We introduce a method for targeting specific cell types that limits disruption of the genes used to gain genetic access to them. In addition, we show how the method can be used it to selectively target brain cells that express different Hox transcription factor genes. These developmentally important genes are expressed in cell types located in anatomically distinct regions along the anterior-posterior axis of the fly nervous system. Our method thus can be used to target specific regions of the nervous system, as well as specific cell types within them, using combinatorial methods.

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Photo by Steve Johnson on Unsplash

Photo by Steve Johnson on Unsplash

Why is it important?

We introduce a unique method for capturing the regulatory information needed to express a particular gene without perturbing the expression of the gene and its protein product. Our method uses what are called split inteins, which can join two protein fragments to make a whole protein. Split inteins have typically been used to join two halves of a particular split protein of interest, but the split inteins introduced in our method act generally and can join many different split proteins.

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