Mammalian hair follicles develop from a series of complex interactions between the epidermis and the underlying dermis. One family of genes potentially important in this process is the Msx homeobox genes which have been shown to be important in mediating epithelial-mesenchymal interactions during mammalian organogenesis. Msx2-deficient mice exhibit tooth, stomach, mammary gland, growth plate and most noticeably, hair and skin phenotypes. Msx2 null mice are born and appear normal compared to their littermates until postnatal day 15, then exhibit progressive balding from head to tail. Several defects were observed in Msx2 mutant skin and hair. The pelage hair on Msx2 null mice will grown back if they are fed with a proteinous liquid diet, only to epilate again in 10 days. We examined the expression pattern of both Msx1 and Msx2 during the first hair cycle using in situ hybridization. Both Msx1 and Msx2 are expressed in the germinative matrix before P8. Thereafter, the expression domain of Msx2 expands to include the inner and possibly the outer root sheath while that of Msx1 remains unchanged. By P17, no Msx1 expression in the hair follicle can be detected whereas Msx2 expression persists. The differences in temporal and spatial expression of Msx1 and Msx2 might explain why Msx1 fails to compensate for the Msx2 mutation in the hair follicle. Functional redundancy between Msx1 and Msx2 during organogenesis is further supported by the generation of mice deficient for both Msx1 and Msx2 in which development of numerous organs in the body is affected. Hair follicle development in double mutant embryos is affected at the follicle induction stage in which only one third the number of follicles are induced compared to wild-type embryos. Expression of the epidermal marker Sonic Hedgehog (shh) and dermal marker Patched (ptc) in double mutant skin appears comparable to wild type, however, the number of shh and ptc expression sites is reduced. We propose that Msx genes play important roles in both early follicle induction process and in later hair growth cycles.
