Genomics of impaired healing models in Drosophila: Searching for a unique pathway?

FEDERICO PRADA; A CHERNOMORETZ; R LEEMMANS; E MARTÍN BLANCO; O PODHAJCER

Madrid

Simposio; Regeneracion de Heridas; 2007

CIEMAT

Wound healing is an intricate natural process that is orchestrated by many different cell types and numerous extracellular molecules that surround the injured area. Nevertheless, the role of most of the components has been difficult to establish. To study the biology of healing we used the Drosophila model that has been proposed as an appropriate system to follow morphogenetic movements, like the dorsal closure which resembles a healing process in flies. Previous studies have shown that the JNK pathway is deeply implicated in the dorsal closure. Interestingly, the same phenotypes can be generated by modifying certain molecules beyond the plasmatic membrane. SPARC is a matricellular protein that regulates cell shape, adhesion, proliferation, migration and differentiation. SPARC overexpression in Drosophila embryos led to impairment of dorsal closure, a phenotype very similar to that observed previously with JNK mutants. Since both SPARC and JNK were involved in vertebrates wound healing process, we performed global gene expression analysis to identify genes participating in the impaired Drosophila dorsal closure in both models. The comparison between differentially expressed genes in both models showed no clear homology. Moreover, the amount of genes and fold changes in gene activity in the HEP model were much larger than those observed in the SPARC model. Our data demonstrate that several pathways acting or not in parallel can lead to the same phenotype and might be implicated in different stages of the healing process. Moreover, SPARC might be acting in more specific and subtle stages of dorsal closure and vertebrate wound healing.