Comment

Developmental abnormalities of the gastrointestinal tract are an important cause of morbidity in infants. Oesophageal atresia (incidence 1 in 2000 live births), Hirschsprung’s disease (1 in 5000), and duodenal atresia form much of the case work of a paediatric surgeon, yet virtually nothing is known about the molecular mechanisms that control gastrointestinal morphology. The article by Kaestner et al is the first to show how a regulatory gene in the embryo can alter gastrointestinal structure. They report morphological changes in the development of villi in the upper small intestine and the stomach epithelia.

Mesenchymal cells adjacent to the endoderm are central to the normal ontogeny of the gastrointestinal epithelium.^1 2Kaestner et al examined a regulatory protein,Fkh6 (Forkhead homolog 6), which is expressed only in the mesenchyme adjacent to the developing endoderm that is destined to become epithelium. Fkh6 was therefore a candidate gene in the regulation of gastrointestinal development.3 Fkh6 is a member of the winged helix family of transcription factors, so called because of their appearance when bound to the DNA whose transcription they regulate.4

Fkh6 was deleted from the genome of embryonic stem cells by targeting the gene with a …