SPARC is a highly conserved trimodular Ca2+- and Collagen-binding matricellular protein with diverse functions during development, wound healing and cancer metastasis. Our lab previously generated an embryonic lethal Drosophila SPARC null mutant, Df(3R)nm136, analysis of which revealed that SPARC was required for the deposition of Collagen IV into basal laminae and normal nervous system development during embryogenesis. In contrast to these previous studies, my data revealed that SPARC is not required for the deposition of Collagen IV into embryonic basal laminae or embryonic nervous system development. Further analysis showed that the Df(3R)nm136 chromosome carried a second-site mutation in the Neuralized locus which caused the nervous system defects and embryonic lethality previously associated with a loss of SPARC. Removal of this second site mutation and reanalysis of the SPARC mutant phenotype revealed that SPARC is required for larval development where it appears to play a role in the regulation fat body remodelling. SPARC mutant fat bodies showed changes in cell shape and basal lamina remodelling which resemble the fat body remodelling process that normally occurs during pre-pupal stages via up-regulation of MMP2 in response to the steroid hormone ecdysone. The effects of loss of SPARC on fat body cells were shown to be cell autonomous. Structure-function analysis of SPARC showed that secretion of SPARC is required for its function, whereas Domain1 is dispensable. Together, my studies indicate that SPARC has essential intra and extracellular roles during Drosophila larval fat body development.
Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/32083 |
Date | 19 January 2012 |
Creators | Shahab, Jaffer |
Contributors | Ringuette, Maurice |
Source Sets | University of Toronto |
Language | en_ca |
Detected Language | English |
Type | Thesis |
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