Disruption of the IP₃ receptor gene of Drosophila affects larval metamorphosis and ecdysone release

Abstract

Background: The inositol 1,4,5-trisphosphate (IP₃) receptor is an intracellular calcium channel that couples cell membrane receptors, via the second messenger IP₃, to calcium signal transduction pathways within many types of cells. IP₃ receptor function has been implicated in development, but the physiological processes affected by its function have yet to be elucidated. In order to identify these processes, we generated mutants in the IP₃ receptor gene (itpr) of Drosophila and studied their phenotype during development. Results: All itpr mutant alleles were lethal. Lethality occurred primarily during the larval stages and was preceded by delayed moulting. Insect moulting occurs in response to the periodic release of the steroid hormone ecdysone which, in Drosophila is synthesised and secreted by the ring gland. The observation of delayed moulting in the mutants, coupled with expression of the IP₃ receptor in the larval ring gland led us to examine the effect of the itpr alleles on ecdysone levels. On feeding ecdysone to mutant larvae, a partial rescue of the itpr phenotype was observed. In order to assess ecdysone levels at all larval stages, we examined transcripts of an ecdysone-inducible gene, E74; these transcripts were downregulated in larvae expressing each of the itpr alleles. Conclusions: Our data show that disruption of the Drosophila IP₃ receptor gene leads to lowered levels of ecdysone. Synthesis and release of ecdysone from the ring gland is thought to occur in response to a neurosecretory peptide hormone secreted by the brain. We propose that this peptide hormone requires an IP₃ signalling pathway for ecdysone synthesis and release in Drosophila and other insects. This signal transduction mechanism which links neuropeptide hormones to steroid hormone secretion might be evolutionarily conserved.