Expression of differentiation markers during fetal skin development in humans: Immunohistochemical studies on the precursor proteins forming the cornified cell envelope

The cornified cell envelope is formed during the terminal differentiation o f epidermis through crosslinking of specific proteins by transglutaminases. The specific arrangement of individual protein in the cornified cell envel ope and participation of individual protein in the cornified cell envelope at different regions of skin, i.e., palm, foreskin, lips, etc. are not clea rly understood. In order to understand the pattern and expression schedule of each individual precursor protein during the differentiation and formati on of cornified cell envelope, the expression of precursor proteins in deve loping hut-nan fetal skins from the first to the third trimester were exami ned by immunohistochemical studies. Involucrin was found in the periderm an d intermediate layer from 14 wk estimated gestational age, while loricrin a nd small proline-rich protein 1 were found in the periderm from 16 wk estim ated gestational age. Filaggrin and trichohyalin that are absent in the adu lt cornified cell envelope were found in the granular and horny layers from 24 wk estimated gestational age. The precursor proteins except trichohyali n did not change their patterns after the onset of initial expression durin g development. Trichohyalin was transiently expressed in the granular and h orny layers of the epidermis from 24 wk estimated gestational age with peak expression at 27 wk estimated gestational age, but was not detected in adu lt skin. In hair follicles, trichohyalin expression was stable without chan ge from 20 wk estimated gestational age. These findings suggest that fetal skin may have different sets of barriers from the second trimester; the imm ature cornified cell envelope is formed in the early second trimester and t he mature cornified cell envelope is formed in the late second or early thi rd trimester when filaggrin and trichohyalin appear.