Richardson, Rebecca ORCID: 0000-0002-4701-8713, Metzger, Manuel, Knyphausen, Philipp, Ramezani, Thomas ORCID: 0000-0003-4681-7844, Slanchev, Krasimir, Kraus, Christopher, Schmelzer, Elmon and Hammerschmidt, Matthias (2016). Re-epithelialization of cutaneous wounds in adult zebrafish combines mechanisms of wound closure in embryonic and adult mammals. Development, 143 (12). S. 2077 - 2089. CAMBRIDGE: COMPANY OF BIOLOGISTS LTD. ISSN 1477-9129

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Abstract

Re-epithelialization of cutaneous wounds in adult mammals takes days to complete and relies on numerous signalling cues and multiple overlapping cellular processes that take place both within the epidermis and in other participating tissues. Re-epithelialization of partial- or full-thickness skin wounds of adult zebrafish, however, is extremely rapid and largely independent of the other processes of wound healing. Live imaging after treatment with transgene-encoded or chemical inhibitors reveals that re-epithelializing keratinocytes repopulate wounds by TGF-beta- and integrin-dependent lamellipodial crawling at the leading edges of the epidermal tongue. In addition, re-epithelialization requires long-range epithelial rearrangements, involving radial intercalations, flattening and directed elongation of cells - processes that are dependent on Rho kinase, JNK and, to some extent, planar cell polarity within the epidermis. These rearrangements lead to a massive recruitment of keratinocytes from the adjacent epidermis and make re-epithelialization independent of keratinocyte proliferation and the mitogenic effect of FGF signalling, which are only required after wound closure, allowing the epidermis outside the wound to re-establish its normal thickness. Together, these results demonstrate that the adult zebrafish is a valuable in vivo model for studying and visualizing the processes involved in cutaneous wound closure, facilitating the dissection of direct from indirect and motogenic from mitogenic effects of genes and molecules affecting wound re-epithelialization.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Richardson, RebeccaUNSPECIFIEDorcid.org/0000-0002-4701-8713UNSPECIFIED
Metzger, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knyphausen, PhilippUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramezani, ThomasUNSPECIFIEDorcid.org/0000-0003-4681-7844UNSPECIFIED
Slanchev, KrasimirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraus, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmelzer, ElmonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hammerschmidt, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-272195
DOI: 10.1242/dev.130492
Journal or Publication Title: Development
Volume: 143
Number: 12
Page Range: S. 2077 - 2089
Date: 2016
Publisher: COMPANY OF BIOLOGISTS LTD
Place of Publication: CAMBRIDGE
ISSN: 1477-9129
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EPITHELIAL-MESENCHYMAL TRANSITION; HUMAN KERATINOCYTE MIGRATION; GROWTH-FACTOR-BETA; TRANSGENIC ZEBRAFISH; CELL POLARITY; TGF-BETA; INFLAMMATORY RESPONSE; EXTENSION MOVEMENTS; INTEGRIN RECEPTORS; SIGNALING PATHWAYSMultiple languages
Developmental BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27219

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