The role of the stubble protease in RhoA signaling during Drosophila imaginal disc morphogenesis

Keywords

Cell differentiation, Drosophila melanogaster -- Genetics, Drosophila melanogaster -- Morphogenesis

Abstract

The epithelial morphogenesis of imaginal discs of Drosophila melanogaster is controlled by multiple genes and the steroid hormone 20-hydroxy ecdysone. Some of the genes required for epithelial morphogenesis are ecdysone responsive whereas others are not. The RhoA signal transduction pathway plays a critical role in leg and wing imaginal disc development, yet the individual components of this pathway are not responsive to ecdysone. This raises the important question of how non-ecdysone responsive gene products interact ·with those that are induced by ecdysone to control imaginal disc morphogenesis. One ecdysone gene with a critical role in leg and wing morphogenesis is the Stubble-stubbloid (Sb-sbd) locus. The Sb-sbd gene product is a type II transmembrane serine protease (TTSP) with an extracellular proteolytic domain. Mutations in Sb-sbd interact genetically with mutations in genes encoding RhoA pathway members, suggesting a biochemical relationship between the ecdysone responsive Sb-sbd locus and the non-ecdysone RhoA pathway during leg and wing morphogenesis. At present the exact nature of the relationship is unclear. Some evidence supports a regulatory role for Sb-sbd in the RhoA pathway, whereas other evidence suggests that Sb-sbd is a downstream transcriptional target of RhoA signaling. The goal of this thesis is to attempt to distinguish between these two possibilities. In a gain-of-function assay I show that the serine residue in the catalytic triad of the Sb-sbd serine protease is essential for the observed interactions supporting previously published observations that Sb-sbd

proteolytic activity is essential for leg and wing morphogenesis. I also show Sb-sbd interacts with the apex of the RhoA hierarchy but not with downstream effector molecules in this gain-of-function assay. My data also show that the endogenous Sb-sbd protein is non-abundant and it has a very short half life when expressed ectopically. These features are consistent with a possible role as a temporal regulator of RhoA signaling. Finally, the ubiquitous expression of a UAS-Sb transgenic construct using an actin or P-tubulin GAL4 driver led to early lethality, and the ectopic expression of UASSb by the epidermal 69B GAL4 driver resulted in a Dachsous like leg phenotype. These results imply that Sb-sbd is regulated in a highly temporal and tissue-specific manner and suggest a tentative link between Sb-sbd protease activity and cadherin function.

Notes

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Graduation Date

2004

Degree

Master of Science (M.S.)

College

College of Arts and Sciences

Format

PDF

Pages

61 p.

Language

English

Length of Campus-only Access

None

Access Status

Masters Thesis (Open Access)

Identifier

DP0029487

Subjects

Arts and Sciences -- Dissertations, Academic; Dissertations, Academic -- Arts and Sciences

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