論文 - 詳細
| RRC ID | 47912 |
|---|---|
| 著者 | Álvarez-Fernández C, Tamirisa S, Prada F, Chernomoretz A, Podhajcer O, Blanco E, Martín-Blanco E. |
| タイトル | Identification and functional analysis of healing regulators in Drosophila. |
| ジャーナル | PLoS Genet |
| 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. |
| 巻・号 | 11(2) |
| ページ | e1004965 |
| 公開日 | 2015-2-3 |
| DOI | 10.1371/journal.pgen.1004965 |
| PII | PGENETICS-D-14-01610 |
| PMID | 25647511 |
| PMC | PMC4315591 |
| MeSH | Actins / genetics* Actins / metabolism Animals Cytoskeleton / genetics* Cytoskeleton / pathology Drosophila melanogaster Epithelium / growth & development Epithelium / metabolism Gene Expression Regulation Genome, Insect Humans Imaginal Discs / growth & development Imaginal Discs / metabolism* Imaginal Discs / pathology JNK Mitogen-Activated Protein Kinases / genetics MAP Kinase Signaling System / genetics Regeneration / genetics Signal Transduction Thorax / growth & development Thorax / metabolism Thorax / pathology Wound Healing / genetics* |
| IF | 5.175 |
| 引用数 | 3 |
| WOS 分野 | GENETICS & HEREDITY |
| リソース情報 | |
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