CONICET | Buscador de Institutos y Recursos Humanos

Wound healing is a natural process orchestrated by many different cell types and molecules. Nevertheless, the precise role of most of the components has been difficult to establish. As a result of a global gene expression study to identify phylogenetically conserved genes involved in wound healing, the gene SPARC was shown to be a relevant participant in all of our consortium studied models, that included two mice strains, humanized skin, human organotypic cultures and Drosophila imaginal disc cultures. SPARC, an ECM component involved in cell-shape change, adhesion, proliferation, migration and differentiation, was seen down-regulated during the normal healing process in all models. For this reason, we decided to engineer a transgenic fly to overexpress SPARC in Drosophila (dSPARC) as an impaired healing model. SPARC gain of function in ectoderm and in the whole embryo affected dramatically the dorsal closure, producing a phenotype very similar to that observed with JNK mutants. Moreover, dSPARC overexpression showed homophilic cell adhesion anomalies, diminishing levels of focal contacts and inhibition of cytoskeleton rearrangement all over the dorsal closure leading edge. Analysis of the full transcriptome of whole embryos overexpressing dSPARC resulted in a group of 26 differentially expressed genes. Ontologic analysis showed the following biological functions overrepresented: membrane trafficking, PI3K pathway, cytoskeleton remodelling, lipid homeostasis and immune response. We validated the use of SPARC gain of function as a model of impaired healing and moreover, our data confirmed the importance of a gene implicated in adhesion and cell shape changes in the physiology of dorsal closure movement.