THE EFFECTS OF THE GLUCOCORTICOID, DEXAMETHASONE, ON THE DEVELOPMENT OF THE DROSOPHILA EMBRYO

We have investigated the effects of the glucocorticoid, dexamethasone, and five structural analogs on Drosophila development in an effort to identify steroid ligands that may play a role in the embryogenesis of this organism. Embryos were exposed to glucocorticoids either by dire ct culture in supplemented medium, or by examining embryos from adult flies raised on supplemented fly food. After exposure, embryos were ex amined for developmental defects. At a morphological level, exposure t o dexamethasone disrupts the dorsolateral folding of the amnioserosa d uring germ band extension. In addition, germ band retraction and dorsa l closure is also disrupted. The phenocritical period of these effects is within the first 4 h of embryogenesis. This response is dosage sen sitive, with embryos responding to concentrations of dexamethasone ran ging from 10(-6) to 10(-3)M. Furthermore, glucocorticoids which are cl osely related structural analogs of dexamethasone also disrupt germ ba nd retraction and dorsal closure, while other tested steroids had no e ffect on embryonic development. At a molecular level, expression of th e gene, Kruppel, is absent from the amnioserosa of dexamethasone-treat ed embryos. The cuticular phenocopy resulting from exposure to dexamet hasone and related glucocorticoids is morphologically similar to the m utant phenotype associated with four genes required for germ band retr action, namely hindsight, serpent, tail-up and u-shaped. The results o f this study represent the first association of a glucocorticoid with dose, stage and tissue specific effects on Drosophila development at b oth morphological and molecular levels.