Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Grainy head target genes in epithelial morphogenesis and wound healing
Stockholm University, Faculty of Science, The Wenner-Gren Institute . (Christos Samakovlis)
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 [en]
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: urn:nbn:se:su:diva-38377ISBN: 978-91-7447-004-8 (print)OAI: oai:DiVA.org:su-38377DiVA: diva2:311020
Public defence
2010-05-21, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
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
List of papers
1. Grainy head regulates genes involved in cuticle maturation and immune response in Drosophila.
Open this publication in new window or tab >>Grainy head regulates genes involved in cuticle maturation and immune response in Drosophila.
(English)Manuscript (preprint) (Other academic)
Identifiers
urn:nbn:se:su:diva-38596 (URN)
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2010-04-26Bibliographically approved
2. Septate-Junction-Dependent Luminal Deposition  of Chitin Deacetylases Restricts  Tube Elongation in the Drosophila Trachea
Open this publication in new window or tab >>Septate-Junction-Dependent Luminal Deposition  of Chitin Deacetylases Restricts  Tube Elongation in the Drosophila Trachea
Show others...
2006 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 16, no 2, 180-185 p.Article in journal (Refereed) Published
Abstract [en]

The function of tubular epithelial organs like the kidney and lung is critically dependent on the length and diameter of their constituting branches. Genetic analysis of tube size control during Drosophila tracheal development has revealed that epithelial septate junction (SJ) components and the dynamic chitinous luminal matrix coordinate tube growth. However, the underlying molecular mechanisms controlling tube expansion so far remained elusive. Here, we present the analysis of two luminal chitin binding proteins with predicted polysaccharide deacetylase activities (ChLDs). ChLDs are required to assemble the cable-like extracellular matrix (ECM) and restrict tracheal tube elongation. Overexpression of native, but not of mutated, ChLD versions also interferes with the structural integrity of the intraluminal ECM and causes aberrant tube elongation. Whereas ChLD mutants have normal SJ structure and function, the luminal deposition of the ChLD requires intact cellular SJs. This identifies a new molecular function for SJs in the apical secretion of ChLD and positions ChLD downstream of the SJs in tube length control. The deposition of the chitin luminal matrix first promotes and coordinates radial tube expansion. We propose that the subsequent structural modification of chitin by chitin binding deacetylases selectively instructs the termination of tube elongation to the underlying epithelium.

Research subject
Developmental Biology
Identifiers
urn:nbn:se:su:diva-32565 (URN)10.1016/j.cub.2005.11.074 (DOI)
Available from: 2009-12-14 Created: 2009-12-14 Last updated: 2017-12-12Bibliographically approved
3. The tyrosine kinase Stitcher activates Grainy head and epidermal woundhealing in Drosophila.
Open this publication in new window or tab >>The tyrosine kinase Stitcher activates Grainy head and epidermal woundhealing in Drosophila.
Show others...
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.

Identifiers
urn:nbn:se:su:diva-38598 (URN)doi:10.1038/ncb1898 (DOI)000267603100019 ()
Available from: 2010-04-20 Created: 2010-04-20 Last updated: 2017-12-12Bibliographically approved

Open Access in DiVA

fulltext(958 kB)1611 downloads
File information
File name FULLTEXT01.pdfFile size 958 kBChecksum SHA-512
048dca7923e24e9835ef2ea262963fb75a6a54fbb3482fcdbe1b40aacfc1fb8fdd44cc15aa760c21eaf81f23967155272cb79f1c5b015b01ba08bcec923d46bb
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Wang, Shenqiu
By organisation
The Wenner-Gren Institute
Developmental Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 1611 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 485 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf