Differences in the levels of Sonic hedgehog protein during early foregut development caused by exposure to Adriamycin give clues to the role of the Shh gene in oesophageal atresia.

Abstract

Sonic hedgehog (Shh) protein is a signalling molecule that is important for defining patterning in the development of vertebrates. Shh has been shown to be involved in the morphogenesis of many organ systems such as notochord, floor plate and limbs and in the development of the left-right axis in vertebrates. In this study we show that high levels of protein occur during the initial period of foregut differentiation into trachea and oesophagus, and that low levels of Shh protein are seen during early development of the foregut where oesophageal atresia and/or tracheo-oesophageal fistula ensue. These studies show that Shh protein is expressed in the rat foregut during embryogenesis, and its level declines as the embryo approaches birth. In adriamycin-treated rats the level of Shh protein expression is very low without any time-dependent changes. These results are consistent with the hypothesis that adriamycin influences the Shh signalling pathway, resulting in disruption of normal development of the foregut.