title: Identification and functional analysis of healing regulators in Drosophila.
abstract: Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response.
authors: Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas. Parc Cientific de Barcelona, Barcelona, Spain.
authors: Carmen
authors: C
authors: Álvarez-Fernández
authors: Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas. Parc Cientific de Barcelona, Barcelona, Spain.
authors: Srividya
authors: S
authors: Tamirisa
authors: Terapia Molecular y Celular, Fundación Instituto Leloir, Buenos Aires, Argentina.
authors: Federico
authors: F
authors: Prada
authors: Departamento de Física, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors: Ariel
authors: A
authors: Chernomoretz
authors: Terapia Molecular y Celular, Fundación Instituto Leloir, Buenos Aires, Argentina.
authors: Osvaldo
authors: O
authors: Podhajcer
authors: Departament de Genètica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Spain.
authors: Enrique
authors: E
authors: Blanco
authors: Instituto de Biología Molecular de Barcelona, Consejo Superior de Investigaciones Científicas. Parc Cientific de Barcelona, Barcelona, Spain.
authors: Enrique
authors: E
authors: Martín-Blanco
mesh_terms: D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003599:Cytoskeleton / Q000235:genetics* / Q000473:pathology; D004331:Drosophila melanogaster; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D005786:Gene Expression Regulation; D049750:Genome, Insect; D006801:Humans; D060227:Imaginal Discs / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction; D013909:Thorax / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000235:genetics*
chemical_list: D000199:Actins; D048031:JNK Mitogen-Activated Protein Kinases
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