APPEARANCE AND DISTRIBUTION OF LAMININ A-CHAIN ISOFORMS AND INTEGRIN ALPHA-2, ALPHA-3, ALPHA-6, BETA-1, AND BETA-4 SUBUNITS IN THE DEVELOPING HUMAN SMALL-INTESTINAL MUCOSA

Background: Laminin, a major component of basement membranes, is well known in its classical heterotrimeric form (B1-A-B2) to regulate diver se biological functions, including cell polarization and differentiati on. However, the role of merosin, a laminin-like molecule in which an M chain is substituted for its homologous A chain, remains largely unk nown. Methods: In the present study, we analyzed by indirect immunoflu orescence the expression and distribution of these four laminin chains as well as the integrins alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, and alpha 6 beta 4, four potential receptors, at the epithelial-me senchymal interface of the developing human small intestine, with a pa nel of specific monoclonal antibodies. Results: Beginning at 7 weeks o f gestation and throughout mucosal organogenesis, the B1 and B2 chains were uniformly detected at the epithelial basement membrane. The A ch ain also was detected beginning at 7 weeks, and its distribution at th e basement membrane remained uniform throughout villus (9 + weeks) and crypt (16 + weeks) formation. In contrast, M chain expression was not observed until 16 weeks; between 16 and 20 weeks, it was exclusively associated with the base of epithelial cells that comprised the formin g crypts. Integrins alpha 6 beta 1 and alpha 6 beta 4, as determined b y their subunit immunolocalization, appeared to be expressed by all en terocytes from 7 to 20 weeks. In contrast, the expression of the alpha 2 beta 1 and alpha 3 beta 1 integrins was found time- and site-restri cted, The alpha 2 subunit was predominantly detected in the epithelial cells of the intervillous area and its derivative, the crypt, whereas the alpha 3 subunit was strongly expressed by all epithelial cells ex cept those located at the bottom of 19-20-week-old crypts. Conclusions : Taken together, these observations demonstrate that both composition al changes in the basement membrane and differential expression of rec eptors occur during human intestinal organogenesis, suggesting that ep ithelial cell-matrix interactions play a role during development. (C) 1995 Wiley-Liss, Inc.