{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:21:51Z","timestamp":1791220911275,"version":"4.1.0"},"reference-count":86,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,5,5]]},"abstract":"<jats:p>Integrins \u03b13\u03b21 and \u03b16\u03b24 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; \u03b16\u03b24 is present in hemidesmosomes, while \u03b13\u03b21 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 \u03b13\u03b21-deficient mice. Examination of extracellular matrix by immunofluorescence microscopy and electron microscopy revealed regions of disorganized basement membrane in \u03b13\u03b21-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 \u03b13\u03b21-deficient skin adhered to laminin-5 through \u03b16 integrins. However, \u03b13\u03b21-deficient keratinocytes spread poorly compared with wild-type cells on laminin-5, demonstrating a postattachment requirement for \u03b13\u03b21 and indicating distinct roles for \u03b13\u03b21 and \u03b16\u03b24. Our findings support a novel role for \u03b13\u03b21 in establishment and\/or maintenance of basement membrane integrity, while \u03b16\u03b24 is required for stable adhesion of the epidermis to the basement membrane through hemidesmosomes.<\/jats:p>","DOI":"10.1083\/jcb.137.3.729","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:47:50Z","timestamp":1027702070000},"page":"729-742","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":354,"title":["\u03b13\u03b21 Integrin Is Required for Normal Development of the Epidermal Basement Membrane"],"prefix":"10.1083","volume":"137","author":[{"given":"C. Michael","family":"DiPersio","sequence":"first","affiliation":[{"name":"*Howard Hughes Medical Institute, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; \u2021Divisions of Nephrology and Newborn Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; and \u00a7Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kairbaan M.","family":"Hodivala-Dilke","sequence":"additional","affiliation":[{"name":"*Howard Hughes Medical Institute, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; \u2021Divisions of Nephrology and Newborn Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; and \u00a7Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Jaenisch","sequence":"additional","affiliation":[{"name":"*Howard Hughes Medical Institute, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; \u2021Divisions of Nephrology and Newborn Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; and \u00a7Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan A.","family":"Kreidberg","sequence":"additional","affiliation":[{"name":"*Howard Hughes Medical Institute, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; \u2021Divisions of Nephrology and Newborn Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; and \u00a7Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard O.","family":"Hynes","sequence":"additional","affiliation":[{"name":"*Howard Hughes Medical Institute, Center for Cancer Research, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; \u2021Divisions of Nephrology and Newborn Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115; and \u00a7Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,5,5]]},"reference":[{"key":"2023072206542142700_B1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/ng0394-299","article-title":"Herlitz's junctional epidermolysis bullosa is genetically linked to mutations in the nicein\/kalinin (laminin 5) LAMC2 gene","volume":"6","author":"Aberdam","year":"1994","journal-title":"Nat Genet"},{"key":"2023072206542142700_B2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/0092-8674(90)90175-E","article-title":"Changes in keratinocyte-extracellular matrix interactions during terminal differentiation: reduction in fibronectin binding precedes loss of \u03b15\u03b21 integrin from the cell surface","volume":"63","author":"Adams","year":"1990","journal-title":"Cell"},{"key":"2023072206542142700_B3","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1083\/jcb.115.3.829","article-title":"Expression of 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