The morphogenetic contributions of SPARC and collagen IV during drosophila embryogenesis

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Shortly after fertilization, multicellular organisms synthesize and secrete a complex mixture of structurally and functionally diverse extracellular matrix (ECM) molecules. In addition to acting as scaffolding for the organization and stability of tissues, ECM molecules regulate cell survival and behavior. Research in my laboratory is focused on using the genetic tractability of the fruit fly Drosophila melanogaster to investigate the contribution of SPARC (Secreted Protein, Acidic, Rich in Cysteine) during embryo development. SPARC is a collagen-binding ECM protein with diverse biological activities. Our studies with Drosophila indicate that SPARC co-localizes with collagen IV in embryonic basal laminae. A basal lamina is a thin sheet of specialized ECM that separates epithelial cells from underlying connective tissue. The interaction of epithelial cells with basal laminae is critical for epithelial cell functions and connective tissue stability. The loss of SPARC expression leads to death during embryonic development due to decreased basal laminae stability and failure of the nervous system to form. We have generated a series of flies that express mutant SPARC using recent advances in genome engineering for the purpose of determining which domain/portion of SPARC is responsible for the embryonic defects. Since a direct interaction between SPARC and collagen IV in basal laminae has been demonstrated in vitro, we are carrying out studies to determine if SPARC and collagen IV interact in vivo. Our data indicate that the neural defects are due to compromised Notch-Delta signaling in the absence of SPARC, underscoring how signal transduction during development is regulated by ECM molecules.