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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

Animals

Blotting

Western

Cells

Cultured

DNA-Binding Proteins

metabolism

Drosophila

enzymology

Drosophila Proteins

genetics

metabolism

Embryo

Nonmammalian

Epidermis

injuries

metabolism

Extracellular Signal-Regulated MAP Kinases

metabolism

Immunohistochemistry

Immunoprecipitation

Phosphorylation

Protein-Tyrosine Kinases

genetics

metabolism

physiology

Transcription Factors

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)