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Mouse cells can regulate genes from fish

Issue date: 10/2/08
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Every cell in your body contains every gene in your genome. So how is it that one set of genes is expressed in your brain, and an entirely different one is expressed in your stomach?

The answer is gene regulation. Using a series of proteins called transcription factors, a cell will turn on only certain genes at certain times. A recent study from Hopkins and the National Institutes of Health shows that gene regulation machinery can be transferred between species.

A team led by Andrew McCallion of the McKusick-Nathans Institute of Genetic Medicine at Hopkins looked at the regulation of a gene called Sox10. The study of regulatory genetic sequences is a growing area of interest in developmental biology.

"These are the 'switches' for genes which tell them when, where and how much gene product is required - they underlie the cellular complexity that is generated from a single complement of genes," McCallion said.

The Sox10 gene is expressed in the developing embryo but is gradually turned off by some cells, particularly in a class of cells called neural crest cells. These are stem cells that will turn into pigment cells in the skin, neurons releasing adrenaline and glia - supporting cells in the nervous system.

"Sox10 is a developmentally critical gene, expressed in many cell types during development and it is mutated in a collection [of] developmental and neurological diseases. We set out to identify the sequences which controlled its function," McCallion said.

Sox10 is important for development because it is a transcription factor that regulates gene expression in neural crest cells. If different genes are turned on in some neural crest cells and turned off in others, this leads to specialization into different cell types. Also, the Sox10 gene itself can be regulated, and the research team found that it could be controlled by DNA close to the Sox10 gene.

The researchers examined how DNA next to the Sox10 gene in mice could affect the regulation of the same gene in zebrafish, which is a well-studied organism in embryology. They hypothesized that regulatory DNA from one species could work in another species.
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