The tyrosine kinase Stitcher activates Grainy head and epidermal wound healing in Drosophila.
Epidermal injury initiates a cascade of inflammation, epithelial remodelling and integument repair at wound sites. The regeneration of the extracellular barrier and damaged tissue repair rely on the precise orchestration of epithelial responses triggered by the injury. Grainy head (Grh) transcription factors induce gene expression to crosslink the extracellular barrier in wounded flies and mice. However, the activation mechanisms and functions of Grh factors in re-epithelialization remain unknown. Here we identify stitcher (stit), a new Grh target in Drosophila melanogaster. stit encodes a Ret-family receptor tyrosine kinase required for efficient epidermal wound healing. Live imaging analysis reveals that Stit promotes actin cable assembly during wound re-epithelialization. Stit activation also induces extracellular signal-regulated kinase (ERK) phosphorylation along with the Grh-dependent expression of stit and barrier repair genes at the wound sites. The transcriptional stimulation of stit on injury triggers a positive feedback loop increasing the magnitude of epithelial responses. Thus, Stit activation upon wounding coordinates cytoskeletal rearrangements and the level of Grh-mediated transcriptional wound responses.
Wang
Shenqiu
S
Department of Developmental Biology, Wenner-Gren Institute, Stockholm University, Sweden.
Tsarouhas
Vasilios
V
Xylourgidis
Nikos
N
Sabri
Nafiseh
N
Tiklová
Katarína
K
Nautiyal
Naumi
N
Gallio
Marco
M
Samakovlis
Christos
C
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D004817:Epidermis / Q000293:injuries* / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C062330:grh protein, Drosophila; D011505:Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases