title: Hole-in-one mutant phenotypes link EGFR/ERK signaling to epithelial tissue repair in Drosophila.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Tissue Morphogenesis and Repair Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Geiger
authors.forename: Lara
authors.initials: L
authors.lastname: Carvalho
authors.forename: Isabel
authors.initials: I
authors.lastname: Campos
authors.forename: Ana Catarina
authors.initials: AC
authors.lastname: Santos
authors.forename: Antonio
authors.initials: A
authors.lastname: Jacinto
mesh_terms: D000205:Actomyosin / Q000378:metabolism; D000483:Alleles; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000201:enzymology / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D004848:Epithelium / Q000196:embryology / Q000201:enzymology / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter / Q000235:genetics; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic; D014945:Wound Healing / Q000235:genetics; D018631:ras Proteins / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C571171:Holn1 protein, Drosophila; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000205:Actomyosin; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins