Gene triggers stem cell differentiation in the intestine

A gene that governs development of neuronal cells has now been shown to be involved in regulating differentiation of stem cells into secretory cells in the intestine.

The research team, which included Howard Hughes Medical Institute investigator Huda Zoghbi, Qi Yang, Nessan Bermingham and Milton Finegold at Baylor College of Medicine, showed that the Math1 gene -- which codes for a gene-activating protein called a transcription factor -- is necessary for the differentiation of three kinds of intestinal cells from stem cells. The team published its findings in the December 7, 2001, issue of the journal Science.

Previous work by Zoghbi and her colleagues revealed Math1s role in governing differentiation of neuronal cells, including sensory cells in the inner ear. In the course of those earlier studies, we detected Math1 expression in the intestine, said Zoghbi. Its function there was unknown. However, we knew that the gut has a nervous system of its own, so we thought Math1 might be important for components of that system, she said.

To pinpoint the genes activity, the researchers genetically engineered mice in which the coding region of the Math1 gene was replaced by an enzyme that would stain the cells expressing the gene in developing mouse embryos. They first examined mice with one copy of the functional Math1 gene, along with the stain-producing gene, to determine which cells expressed Math1.

To our total surprise, we could not detect expression of the gene in the nervous system of the gut, but instead found it in the intestinal epithelium, said Zoghbi. These studies revealed that three kinds of secretory cells expressed Math1. These were goblet cells that secrete mucous important for food movement; enteroendocrine cells that secrete regulatory peptides, and Paneth cells that secrete microbe-fighting pept

Contact: Jim Keeley
Howard Hughes Medical Institute

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