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The tyrosine kinase Stitcher activates Grainy head and epidermal woundhealing in Drosophila.
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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2009 (English)In: Nature Cell Biology, ISSN 1465-7392, E-ISSN 1476-4679, Vol. 11, no 7, 890-895 p.Article in journal (Refereed) Published
Abstract [en]

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 injury1, 2. Grainy head (Grh) transcription factors induce gene expression to crosslink the extracellular barrier in wounded flies and mice3, 4. 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.

Place, publisher, year, edition, pages
2009. Vol. 11, no 7, 890-895 p.
Identifiers
URN: urn:nbn:se:su:diva-38598DOI: doi:10.1038/ncb1898ISI: 000267603100019OAI: oai:DiVA.org:su-38598DiVA: diva2:311147
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Grainy head target genes in epithelial morphogenesis and wound healing
Open this publication in new window or tab >>Grainy head target genes in epithelial morphogenesis and wound healing
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

grainy head (grh) genes encode a family of transcription factors conserved from fly to human. Drosophila grh is the founding member of this gene family and has multiple functions, including tracheal tube size control, epidermal barrier formation and reconstruction after wounding. To understand the underlying molecular mechanism of grh functions, we tried to isolate its direct targets and analyze their function. We identified ten grh targets by combining bioinformatics and genetics. Grh directly controls the expression of stitcher (stit), which encodes a Ret family receptor tyrosine kinase (RTK), during both development and wound healing. Stit promotes actin cable assembly and induces extracellular signal-regulated kinase (ERK) phosphorylation around the wound edges upon injury. Stit also activates barrier repair genes and its own expression at the wound sites in a Grh-dependent manner. This positive feedback loop ensures efficient epidermal wound repair. In addition, Grh regulates the expression of multiple genes involved in chitin biosynthesis or modification. Most of the genes are required for tracheal tube size control. Two of them, verm and serp, encode related putative luminal chitin deacetylases. The functional analysis of verm and serp identifies an important role of luminal chitin matrix modification in limiting tracheal tube elongation. Therefore, it is very likely that Grh controls tracheal tube size through regulating multiple targets involved in the assembly or modification of luminal chitin matrix. Grh also directly activates the epidermal expression of Peptidoglycan recognition protein LC (PGRP-LC) gene that is required for the induction of antimicrobial peptides (AMPs) upon infection. Furthermore, ectopically expressing Grh is sufficient to induce AMP Cecropin A lacZ reporter (CecA-LacZ) in the embryonic epidermis. These results suggest a new function of Grh in the local immune responses in Drosophila barrier epithelia.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2010. 60 p.
Keyword
grh, targets, epidermal wound repair, tracheal tube size control, local immune responses, stit, verm, serp, PGRP-LC, CecA-LacZ
National Category
Developmental Biology
Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-38377 (URN)978-91-7447-004-8 (ISBN)
Public defence
2010-05-21, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
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Note
At the time of the doctoral defense, the following papers was unpublished and had a status as follows: Paper 1: Manuscript. Available from: 2010-04-28 Created: 2010-04-12 Last updated: 2010-04-27Bibliographically approved

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Wang, ShenqiuTsarouhas, VasilisNautiyal, NaumiSamakovlis, Christos
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