Document Detail


ADAM17 transactivates EGFR signaling during embryonic eyelid closure.
MedLine Citation:
PMID:  23211830     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: During mammalian embryonic eyelid closure ADAM17 has been proposed to play a role as a transactivator of epidermal growth factor receptor (EGFR) signaling by shedding membrane bound EGFR ligands. However, ADAM17 also sheds numerous other ligands, thus implicating ADAM17 in additional molecular pathways. The goal of this study was to experimentally establish the role of ADAM17 and determine ADAM17-mediated pathways essential for the embryonic eyelid closure.
METHODS: Wild-type (WT) and woe mice, carrying a hypomorphic mutation in Adam17, were evaluated using H&E and scanning electron microscopy. Expressions of ADAM17, EGFR, and the phosphorylated form EGFR-P were evaluated using immunohistochemistry. BrdU and TUNEL assays were used to evaluate cell proliferation and apoptosis, respectively. In vitro scratch assays of primary cultures were used to evaluate cell migration. Clinical and histologic analyses established if the hypermorphic Egfr(Dsk5) allele can rescue the woe embryonic eyelid closure.
RESULTS: woe mice exhibited a failure to develop the leading edge of the eyelid and consequently failure of the embryonic eyelid closure. Expression of ADAM17 was identified in the eyelid epithelium in the cells of the leading edge. ADAM17 is essential for epithelial cell migration, but does not play a role in proliferation and apoptosis. EGFR was expressed in both WT and woe eyelid epithelium, but the phosphorylated EGFR-P form was detected only in WT. The Egfr(Dsk5) allele rescued woe eyelid closure defects, but also rescued woe anterior segment defects and the absence of meibomian glands.
CONCLUSIONS: We provide in vivo genetic evidence that the role of ADAM17 during embryonic eyelid closure is to transactivate EGFR signaling.
Authors:
Eryn L Hassemer; Bradley Endres; Joseph A Toonen; Adam Ronchetti; Richard Dubielzig; Duska J Sidjanin
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-07
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-08     Completed Date:  2013-03-05     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  132-40     Citation Subset:  IM    
Affiliation:
Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
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MeSH Terms
Descriptor/Qualifier:
ADAM Proteins / genetics,  metabolism*
Animals
Cell Death / physiology
Cell Movement / physiology
Cell Proliferation
Eyelids / abnormalities,  cytology,  embryology*,  metabolism*
Female
Gene Expression Regulation, Developmental / physiology
Genotype
Ligands
Male
Meibomian Glands / cytology,  embryology,  physiology
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Phenotype
Pregnancy
Primary Cell Culture
Receptor, Epidermal Growth Factor / metabolism*
Signal Transduction / physiology*
Grant Support
ID/Acronym/Agency:
EY18872/EY/NEI NIH HHS; UL1 TR000055/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Ligands; EC 2.7.10.1/EGFR protein, mouse; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/tumor necrosis factor-alpha convertase
Comments/Corrections

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