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J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/05/729/14 $2.00
Volume 137, Number 3, May 5, 1997 729-742

alpha 3beta 1 Integrin Is Required for Normal Development of the Epidermal Basement Membrane

C. Michael DiPersio,* Kairbaan M. Hodivala-Dilke,* Rudolf Jaenisch,§ Jordan A. Kreidberg,Dagger and Richard O. Hynes*

* Howard Hughes Medical Institute, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Dagger  Divisions of Nephrology and Newborn Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; and § Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Integrins alpha 3beta 1 and alpha 6beta 4 are abundant receptors on keratinocytes for laminin-5, a major component of the basement membrane between the epidermis and the dermis in skin. These integrins are recruited to distinct adhesion structures within keratinocytes; alpha 6beta 4 is present in hemidesmosomes, while alpha 3beta 1 is recruited into focal contacts in cultured cells. To determine whether differences in localization reflect distinct functions of these integrins in the epidermis, we studied skin development in alpha 3beta 1-deficient mice. Examination of extracellular matrix by immunofluorescence microscopy and electron microscopy revealed regions of disorganized basement membrane in alpha 3beta 1-deficient skin. Disorganized matrix was first detected by day 15.5 of embryonic development and became progressively more extensive as development proceeded. In neonatal skin, matrix disorganization was frequently accompanied by blistering at the dermal-epidermal junction. Laminin-5 and other matrix proteins remained associated with both the dermal and epidermal sides of blisters, suggesting rupture of the basement membrane itself, rather than detachment of the epidermis from the basement membrane as occurs in some blistering disorders such as epidermolysis bullosa. Consistent with this notion, primary keratinocytes from alpha 3beta 1-deficient skin adhered to laminin-5 through alpha 6 integrins. However, alpha 3beta 1-deficient keratinocytes spread poorly compared with wild-type cells on laminin-5, demonstrating a postattachment requirement for alpha 3beta 1 and indicating distinct roles for alpha 3beta 1 and alpha 6beta 4. Our findings support a novel role for alpha 3beta 1 in establishment and/or maintenance of basement membrane integrity, while alpha 6beta 4 is required for stable adhesion of the epidermis to the basement membrane through hemidesmosomes.


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