Linked Life Data

10934043

Source:http://linkedlifedata.com/resource/pubmed/id/10934043

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-10-5
pubmed:abstractText
Continuous regeneration and homeostasis of the stratified epidermis requires coordinated regulation of cell proliferation, cell differentiation, and cell survival. Integrin-mediated cell adhesion to the extracellular matrix has important roles in regulating each of these processes. Integrins alpha3beta1 and alpha6beta4 are both receptors on epidermal keratinocytes for the basement membrane protein laminin-5, the major ligand for epidermal adhesion in mature skin. Ablation in mice of either alpha3beta1 or alpha6beta4, through null mutation of the gene encoding the alpha3, alpha6, or beta4 integrin subunit, results in epidermal blistering of varying severity. Our previous studies showed that, despite blistering, differentiation and stratification of the epidermis appeared essentially normal in mice that lacked either alpha3beta1 or alpha6beta4. However, these studies did not definitively address the specific developmental importance of each integrin, since they may have overlapping and/or compensatory functions. Given the individual importance of alpha3beta1 or alpha6beta4 in maintaining the dermo-epidermal junction in mature skin, we sought to determine the importance of these integrins for embryonic skin development and epidermal morphogenesis. In the current study, we analyzed skin development in mutant embryos that completely lack both integrins alpha3beta1 and alpha6beta4. Although alpha3beta1/alpha6beta4-deficient embryos displayed epidermal blistering by stage E15.5 of development, they also retained regions of extensive epidermal adhesion to the basement membrane through stage E16.5, indicating alternative adhesion mechanisms. Apoptosis was induced in detached epidermis of alpha3beta1/alpha6beta4-deficient embryos, exemplifying vividly the importance of epithelial attachment to the basement membrane for cell survival. However, apoptotic cells were completely absent from attached epidermis of alpha3beta1/alpha6beta4-deficient embryos, showing that epithelial adhesion that occurred independently of alpha3beta1 and alpha6beta4 also protected cells from apoptosis. Remarkably, in the absence of the known laminin-5 binding integrins (alpha3beta1, alpha6beta4, and alpha6beta1), keratinocytes retained the capacity to proliferate in the epidermis, and epidermal stratification and skin morphogenesis appeared normal prior to blister formation. These findings show that while alpha3beta1 and alpha6beta4 are both required for integrity of the dermo-epidermal junction, neither one is essential for epidermal morphogenesis during skin development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
113 ( Pt 17)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3051-62
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10934043-Animals, pubmed-meshheading:10934043-Antigens, Surface, pubmed-meshheading:10934043-Apoptosis, pubmed-meshheading:10934043-Basement Membrane, pubmed-meshheading:10934043-Cell Adhesion, pubmed-meshheading:10934043-Cell Adhesion Molecules, pubmed-meshheading:10934043-Cell Division, pubmed-meshheading:10934043-Cell Survival, pubmed-meshheading:10934043-Epidermis, pubmed-meshheading:10934043-Fluorescent Antibody Technique, pubmed-meshheading:10934043-Homeostasis, pubmed-meshheading:10934043-Integrin alpha3beta1, pubmed-meshheading:10934043-Integrin alpha6beta4, pubmed-meshheading:10934043-Integrins, pubmed-meshheading:10934043-Keratinocytes, pubmed-meshheading:10934043-Mice, pubmed-meshheading:10934043-Mice, Knockout, pubmed-meshheading:10934043-Models, Biological, pubmed-meshheading:10934043-Morphogenesis, pubmed-meshheading:10934043-Skin
pubmed:year
2000
pubmed:articleTitle
alpha3beta1 and alpha6beta4 integrin receptors for laminin-5 are not essential for epidermal morphogenesis and homeostasis during skin development.
pubmed:affiliation
Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. dipersm@mail.amc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't