Dynamic expression patterns of tenascin, proteoglycans, and cell adhesion molecules during human hair follicle morphogenesis.

Abstract

The development of skin appendages such as hair, feathers, and teeth is brought about by reciprocal interactions between epidermal and mesenchymal tissues and is thought to be influenced in part by cell adhesion molecules and components of the extracellular matrix. The developmental distributions of tenascin, neural cell adhesion molecule (NCAM), E-cadherin, intercellular adhesion molecule 1 (ICAM-1), chondroitin sulfate proteoglycan (CSPG), and the heparan sulfate proteoglycan perlecan were studied in relation to hair follicle morphogenesis in fetal human skin. Tenascin first appeared in developing skin in focal concentrations at the epidermal-mesenchymal interface, just prior to, and presumably correlated with, hair follicle initiation. Tenascin immunostaining remained prominent in the basement membrane zone and extracellular matrix of the follicle sheath during subsequent morphogenetic stages. Two forms of tenascin (M(r) 250 x 10(3) and 280-300 x 10(3)), were revealed by Western blots of skin extracts. NCAM immunolabeling was initially present throughout the dermis, and became progressively restricted to the dermal condensation and the follicle sheath. Western blot analysis revealed an isoform of NCAM (M(r) 160 x 10(3)) which lacked polysialic acid. At all stages, E-cadherin staining was diminished on follicle cells situated adjacent to the basement membrane, relative to cells in the follicle interior. Follicle-specific immunostaining for ICAM-1 was transient, appearing only at the pre-germ and hair germ stages of development. Antibodies to three distinct CSPG determinants revealed unique immunolabeling patterns following follicle initiation: One CSPG epitope co-distributed with tenascin in the follicle basement membrane and follicle sheath extracellular matrix; one CSPG epitope was similarly expressed, and was also found on follicle epithelial cells; and the third CSPG determinant was noticeably absent from the follicle sheath during elongation of the developing appendage. Perlecan was concentrated in the dermal papilla, in addition to its distribution in all skin basement membranes. A model for how these diverse molecules may interact to influence human hair follicle morphogenesis is presented.