Developmental arrest and ecdysteroid deficiency resulting from mutations at the dre4 locus of Drosophila

Abstract

Loss-of-function mutations of the dre4 gene of Drosophila melanogaster caused stage-specific developmental arrest, the stages of arrest coinciding with periods of ecdysteroid (molting hormone) regulated development. Nonconditional mutations resulted in the arrest of larval development in the first instar; embryogenesis was not impaired, and mutant larvae were behaviorally normal and long-lived. At 31° the temperature-sensitive dre4(e55) allele caused the arrest of larval development in the first or second instars. When upshifted to 31° at various times during development, dre4(e55) mutants exhibited nonpupariation of third-instar larvae, failure of pupal head eversion, failure of adult differentiation, or noneclosion of pharate adults. Under some temperature regimens second-instar larvae pupariated precociously without entering the normally intervening third- instar. Nonpupariation and defects in metamorphosis were associated with the reduction or elimination of ecdysteroid peaks normally associated with late- larval, prepupal, pupal and pharate adult development. Ecdysteroid production by larval ring glands from dre4(e55) hemizygous larvae was suppressed after 2 hr of incubation in vitro at 31°, indicating autonomous expression of the dre4 gene in the ring gland. We postulate that the dre4 gene is required for ecdysteroid production at multiple stages of Drosophila development and that the pathologies observed in dre4 mutants reflect developmental consequences of ecdysteroid deficiency.