Miz1 is required for hair follicle structure and hair morphogenesis

Previous work has implicated the Myc-binding transcription factor Miz1 in the control of keratinocyte proliferation and in the cellular response to TGFbeta. Miz1 is expressed in basal keratinocytes of the interfollicular epidermis and in hair follicles. Here we have conditionally knocked out the POZ/BTB transactivation domain of Miz1 in keratinocytes using a keratin 14 (K14)-Cre mouse deleter strain. K14Cre(+)/Miz1(lox/lox) mice have rough fur as a result of altered hair follicle orientation, irregular hair pigmentation and disturbed hair fiber structure. A regional thickening of the epidermis at the hair funnel orifice was accompanied by suprabasal proliferation, indicating a delayed exit of keratinocytes from the cell cycle. In addition, the catagen of the hair cycle was delayed in K14Cre(+)/Miz1(lox/lox) mice and intrafollicular keratinocyte proliferation was increased. In aged K14Cre(+)/Miz1(lox/lox) animals, the number of hair follicles remained unchanged but the number of visible hairs, especially of zigzag hairs, was reduced and a pigmentary incontinence into the dermis developed. Our data show that Miz1 is involved in controlling proliferation and differentiation in hair follicles and in hair fiber morphogenesis.