Changes in Gap Junction Distribution and Connexin Expression Pattern During Human Fetal Skin DevelopmentKen Aritaa, Masashi Akiyamaa, Yukiko Tsujia, James R. McMillana, Robin A.J. Eadyb, and Hiroshi Shimizuaa Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan b Department of Cell and Molecular Pathology, St John's Institute of Dermatology, King's College, London, United Kingdom Correspondence to: Ken Arita, Dept. of Dermatology, Hokkaido U. Graduate School of Medicine, North 15 West 7, Kita-ku, Sapporo 060-8638, Japan. E-mail: ariken@med.hokudai.ac.jp Gap junctions are intercellular channels composed of connexin subunits that mediate cellcell communication. The functions of gap junctions are believed to be associated with cell proliferation and differentiation and to be important in maintaining tissue homeostasis. We therefore investigated the expression of connexins (Cx)26 and 43, the two major connexins in human epidermis, and examined the formation of gap junctions during human fetal epidermal development. By immunofluorescence, Cx26 expression was observed between 49 and 96 days' estimated gestational age (EGA) but was not present from 108 days' EGA onwards. Conversely, Cx43 expression was observed from 88 days' EGA onwards. Using electron microscopy, the typical structure of gap junctions was observed from 120 days' EGA. The number of gap junctions increased over time and they were more common in the upper layers, within the periderm and intermediate keratinocyte layers rather than the basal layer. Immunoelectron microscopy revealed Cx43 labeling on the gap junction structures after 105 days' EGA. Formation of gap junctions increased as skin developed, suggesting that gap junctions may play an important role in fetal skin development. Furthermore, the changing patterns of connexin expression suggest that Cx26 is important for early fetal epidermal development. (J Histochem Cytochem 50:14931500, 2002) Key Words: connexin 26, connexin 43, electron microscopy, epidermis, fetal skin, gap junction, morphogenesis, periderm
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