RRC ID 15360
著者 Geiger JA, Carvalho L, Campos I, Santos AC, Jacinto A.
タイトル Hole-in-one mutant phenotypes link EGFR/ERK signaling to epithelial tissue repair in Drosophila.
ジャーナル PLoS One
Abstract BACKGROUND:Epithelia act as physical barriers protecting living organisms and their organs from the surrounding environment. Simple epithelial tissues have the capacity to efficiently repair wounds through a resealing mechanism. The known molecular mechanisms underlying this process appear to be conserved in both vertebrates and invertebrates, namely the involvement of the transcription factors Grainy head (Grh) and Fos. In Drosophila, Grh and Fos lead to the activation of wound response genes required for epithelial repair. ERK is upstream of this pathway and known to be one of the first kinases to be activated upon wounding. However, it is still unclear how ERK activation contributes to a proper wound response and which molecular mechanisms regulate its activation.
METHODOLOGY/PRINCIPAL FINDINGS:In a previous screen, we isolated mutants with defects in wound healing. Here, we describe the role of one of these genes, hole-in-one (holn1), in the wound healing process. Holn1 is a GYF domain containing protein that we found to be required for the activation of several Grh and Fos regulated wound response genes at the wound site. We also provide evidence suggesting that Holn1 may be involved in the Ras/ERK signaling pathway, by acting downstream of ERK. Finally, we show that wound healing requires the function of EGFR and ERK signaling.
CONCLUSIONS/SIGNIFICANCE:Based on these data, we conclude that holn1 is a novel gene required for a proper wound healing response. We further propose and discuss a model whereby Holn1 acts downstream of EGFR and ERK signaling in the Grh/Fos mediated wound closure pathway.
巻・号 6(11)
ページ e28349
公開日 2011-11-29
DOI 10.1371/journal.pone.0028349
PII PONE-D-11-05663
PMID 22140578
PMC PMC3226689
MeSH Actomyosin / metabolism Alleles Animals Cell Nucleus / metabolism Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / embryology* Drosophila melanogaster / enzymology Drosophila melanogaster / genetics Embryo, Nonmammalian / cytology Embryo, Nonmammalian / metabolism Enzyme Activation Epithelium / embryology Epithelium / enzymology Epithelium / pathology* ErbB Receptors / metabolism* Extracellular Signal-Regulated MAP Kinases / metabolism* Gene Expression Regulation Gene Knockdown Techniques Genes, Reporter / genetics MAP Kinase Signaling System Models, Biological Mutation / genetics* Nuclear Proteins / genetics* Nuclear Proteins / metabolism Phenotype Protein Transport RNA Interference RNA, Messenger / genetics RNA, Messenger / metabolism Time Factors Transcription, Genetic Wound Healing* / genetics ras Proteins / metabolism
IF 2.74
引用数 15
WOS 分野 CELL BIOLOGY
リソース情報
ショウジョウバエ DGRC#142008