Hair follicle differentiation: expression, structure and evolutionary conservation of the hair type II keratin intermediate filament gene family.

During hair follicle development several cell streams are programmed to differentiate from the cell population of the follicle bulb. In the hair cells, a number of keratin gene families are transcriptionally activated. We describe the characterization of the type II keratin intermediate filament (IF) gene family which is expressed early in follicle differentiation. In sheep wool, four type II IF proteins are expressed. One gene has been completely sequenced and the expression of three of the genes examined in detail. The sequenced gene encodes a 55 x 10(3) Mr protein of the type II keratin IF protein family, designated KII-9 in the new nomenclature we have adopted and described in the Introduction. The gene has a similar exon/intron structure to the epidermal type II keratin IF genes. In situ hybridization experiments show that the genes are expressed in the hair cortical cells but not in the cells of the outer root sheath, inner root sheath or medulla. During hair keratinocyte differentiation the type II IF genes are sequentially activated and coexpressed in the same cells. Expression is first detected in cells in the middle of the follicle bulb located near the dermal papilla and, subsequently, two of the genes are transcriptionally activated in the differentiating keratinocytes as they migrate upwards, in the upper part of the bulb. A fourth type II IF gene is activated later. The genes with the same expression pattern are also closely related in sequence and a number of conserved elements are present in the promoters of those genes, including a novel element which is also found in the promoter of a coexpressed type I IF gene and three other hair keratin genes.