Increased expression of keratin 16 causes anomalies in cytoarchitecture and keratinization in transgenic mouse skin.

The study examined the expression of keratin K14 in human skin, particularly in the epidermis and hair follicles, using monospecific antisera and cRNA probes. It was found that K14 expression and filament organization differed significantly between the hair follicle and epidermis. In the outer root sheath (ORS) cells, which are mitotically active, K14 expression was low, and keratin filaments were fewer and more loosely organized compared to basal epidermal cells. As ORS cells differentiated, they increased K14 expression and formed denser keratin bundles. In contrast, matrix cells, which can differentiate into the inner root sheath, cuticle, and hair shaft, did not express K14 or form keratin filaments. Instead, they produced hair-specific keratins and dense filament bundles without inducing K14 expression. The study suggested that the patterns of K14 expression and filament organization in skin epithelial cells were linked to their pluripotency and highlighted the distinct differentiation programs of hair follicles compared to other stratified squamous epithelia.

The study investigated keratin and keratin mRNA expression during the differentiation of stem cells into epidermis and hair follicles, as well as follicle morphogenesis. It found that type I keratin K14 was expressed early in embryonal basal cells and elevated in the basal layer of developing epidermis, but suppressed in developing matrix cells, indicating a biochemical distinction between diverging cell types. This expression pattern suggested a narrow developmental window for irreversible divergence in basal and matrix cells. In contrast, a hair-specific type I keratin was expressed late in hair matrix development, indicating that keratin expression might be a consequence of cell organization and differentiation rather than a cause.

The study characterized type I keratin genes K16 and K14 on human chromosome 17, finding two genes for K16 and three for K14 in distinct clusters. These genes showed high homology, particularly the K16 genes, which shared similarities in coding sequences and surrounding regions. However, only one K16 gene produced a functional protein capable of forming keratin filaments, likely due to a stronger promoter. The functional K16 gene was confirmed to be responsible for K16 expression in human tissues using a specific polyclonal antiserum.

The study characterized the human type I keratins K16 and K14, which were coexpressed in various epithelial tissues, including hair follicles. Researchers identified two genes for K16 and three for K14 on chromosome 17, noting that these genes were tightly linked and part of recently duplicated genome segments. Despite strong homology between the two K16 genes, only one encoded a functional protein capable of forming keratin filaments, likely due to a weaker promoter in the non-functional gene. A polyclonal antiserum was developed to specifically recognize the functional K16 gene product, confirming its expression in human tissues.

The study analyzed keratins and filaggrin in over 50 samples of human embryonic and fetal skin, identifying four periods of epidermal development: embryonic, stratification, follicular keratinization, and interfollicular keratinization. Keratins of 50 and 58 kD were consistently present, while 56.5 and 67 kD keratins appeared during stratification and increased with development. Filaggrin was first detected at 15 weeks, associated with keratinizing cells around hair follicles, and later in the granular and cornified layers. The findings indicated a relationship between protein expression and epidermal morphologic changes, with keratin expression marking tissue commitment to stratification and keratinization, and no unique "fetal" keratins were identified.