Periderm cells form cornified cell envelope in their regression process during human epidermal development

Terminally differentiated stratified squamous epithelium forms a lining of the plasma membrane called the cornified cell envelope, a thick layer of se veral covalently cross-linked precursor proteins including involucrin, smal l proline-rich proteins, and loricrin, Their cross-linking isodipeptide bon ds are formed by epidermal transglutaminases 1-3, Material from lamellar gr anules is attached on the extracellular surface of corneocytes during the k eratinization process. The formation of cornified cell envelope and sequent ial expression of major cornified cell envelope precursor proteins, transgl utaminases, and 25 kDa lamellar granule-associated protein were studied in human embryonic and fetal skin. Ultrastructurally, membrane thickening has already started in periderm cells of the two-layered epidermis and an elect ron-dense, thickened cell envelope similar to cornified cell envelope in ad ult epidermis is observed in periderm cells at the three-layered and later stages of skin development. In the two-layered epidermis (49-65 d estimated gestational age), immunoreactivities of involucrin, small proline-rich pro teins, all the transglutaminases, and lamellar granule-associated protein w ere present only in the periderm, In the three-layered epidermis and therea fter (66-160 d estimated gestational age), loricrin became positive in the periderm cells, transglutaminases extended to the entire epidermis, and lam ellar granule-associated protein was detected in intermediate cells as well as periderm cells. Immunoelectron microscopy demonstrated that both major cornified cell envelope precursor proteins, involucrin and loricrin, were r estricted to the cornified cell envelope in periderm cells at this stage of development. After 160 d estimated gestational age, the periderm had disap peared and cornified cell envelope proteins and lamellar granule-associated proteins were expressed in the spinous, granular, and cornified cells and transglutaminases were detected in the entire epidermis. These findings ind icate that cornified cell envelope precursor proteins, transglutaminases, a nd lamellar granule-associated proteins are expressed in coordination in pe riderm cells during human epidermal development and suggest that periderm c ells form cornified cell envelope in the process of regression.