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© The Rockefeller University Press,
0021-9525/2000//1149 $5.00
The Journal of Cell Biology, Volume 150, Number 5,
, 2000 1149-1160
Original Article |
Conditional Ablation of β1 Integrin in Skin
: Severe Defects in Epidermal Proliferation, Basement Membrane Formation, and Hair Follicle Invagination
Howard Hughes Medical Institute, Dept. of Molecular Genetics and Cell Biology, The University of Chicago, 5841 S. Maryland Ave., Rm. N314, Chicago, IL 60637.(773) 702-0141(773) 702-1347
lain{at}midway.uchicago.edu
The major epidermal integrins are
3β1 and hemidesmosome-specific 6β4; both share laminin 5 as ligand. Keratinocyte culture studies implicate both integrins in adhesion, proliferation, and stem cell maintenance and suggest unique roles for β1 integrins in migration and terminal differentiation. In mice, however, whereas ablation of 6 or β4 results in loss of hemidesmosomes, epidermal polarity, and basement membrane (BM) attachment, ablation of 3 only generates microblistering due to localized internal shearing of BM. Using conditional knockout technology to ablate β1 in skin epithelium, we have uncovered biological roles for β1 integrins not predicted from either the 3 knockout or from in vitro studies. In contrast to 3 null mice, β1 mutant mice exhibit severe skin blistering and hair defects, accompanied by massive failure of BM assembly/organization, hemidesmosome instability, and a failure of hair follicle keratinocytes to remodel BM and invaginate into the dermis. Although epidermal proliferation is impaired, a spatial and temporal program of terminal differentiation is executed. These results indicate that β1's minor partners in skin are important, and together, β1 integrins are required not only for extracellular matrix assembly but also for BM formation. This, in turn, is required for hemidesmosome stability, epidermal proliferation, and hair follicle morphogenesis. However, β1 downregulation does not provide the trigger to terminally differentiate.
Key Words: integrins • epidermis • conditional • knockout • proliferation • skin
© 2000 The Rockefeller University Press
Abbreviations used in this paper: BL, basal layer; BM, basement membrane; bs, backskin; DEJ, dermal–epidermal junction; ECM, extracellular matrix; ES, embryonic stem; GR, granular; LD, lamina densa; SC, stratum corneum; SP, spinous; WT, wild-type.
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