INVESTIGADORES
LLERA Andrea Sabina
congresos y reuniones científicas
Título:
Overexpression of the dSPARC gene impairs wound healing in Drosophila melanogaster
Autor/es:
PRADA, FEDERICO; CHERNOMORETZ, ARIEL; ALVAREZ-FERNANDEZ, C; LLERA ANDREA S; WAPPNER, PABLO; MARTIN BLANCO, E; PODHAJCER, OSVALDO
Lugar:
Chicago IL
Reunión:
Conferencia; 50th Annual Drosophila Research Conference; 2009
Resumen:
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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.