RUGGIERO, R.P*; VON KALM, L.; University of Central Florida; University of Central Florida: Genetic analysis of the intersection between ecdysone and intracellular signaling during Drosophila leg and wing morphogenesis
Epithelial morphogenesis is a critical process in the metamorphosis of holometabolis insects, and the product of coordinated endocrine, paracrine, and intracellular signaling events. Our work, and the work of others, has revealed an intersection between the systemic steroid hormone 20-hydroxy ecdysone (ecdysone), and the intracellular RhoA signaling pathway in the developing leg and wing imaginal discs of Drosophila melanogaster. Imaginal discs are composed of single cell-thick epithelia that undergo extensive reconfigurations to form rudimentary adult organs at the onset of metamorphosis. Ecdysone directs all major post-embryonic developmental transitions in Drosophila by inducing concerted, tissue-specific cascades of gene expression. The mechanisms underlying how global ecdysone signaling induces tissue-specific responses are not well understood. RhoA is a highly-conserved intracellular regulator of changes in the cytoskeleton, transcription, cell growth, cell shape, and cell division at all stages of development. The ecdysone-inducible Stubble locus encodes a type II transmembrane serine protease that appears to link the ecdysone and RhoA pathways in leg and wing imaginal discs. Strong Stubble mutant alleles produce severe leg and wing malformations when homozygous or combined with mutant alleles of activators in the RhoA signaling pathway. We demonstrate that mutant alleles of known negative regulators of RhoA reduce the frequency and severity of malformations seen in RhoA/Stubble double mutants. Our data suggest that the Stubble gene functions as an ecdysone-induced trigger of intracellular RhoA signaling during the process of imaginal disc morphogenesis. This provides a model of how a global hormone signal can act through a ubiquitous intracellular signaling pathway to elicit appropriate tissue-specific responses.
