Implications of constitutively active bone morphogenetic protein (BMP) signaling in skin morphogenesis and skin postnatal homeostasis

2011-12-13The skin and its array of epidermal appendages with their complex 3-dimensional structure provide an excellent model in which to study morphogenesis, pattern formation, and homeostasis. The biochemical signals that govern these biological processes continue to be unraveled. Bone Morphogenetic Proteins (BMP) play an integral role in both morphogenesis and homeostasis of the epidermis, however the precise details of this role remains a source of inquiry. ❧ To further study the role of BMP signaling in the epidermis and its appendages both in morphogenesis and homeostasis we have generated transgenic mice harboring a constitutively active form of the BMPR1A receptor under a Keratin 14 (K14) promoter. This will drive expression of the transgene in the basal layer of the epidermis as well as the Outer Root Sheath (ORS) of the hair follicle. ❧ At strong levels of transgene expression hair follicle morphogenesis is markedly impaired. Epidermal morphogenesis appeared normal, though the balance of differentiation and proliferation was perturbed. Interestingly, in the animals which expressed low levels of the K14Alk3 transgene, there was a progressive loss hair with age. This loss of hair follicle homeostasis implicates BMP as not only a crucial player in morphogenesis, but important in finely balancing proliferation and quiescence in the hair follicle stem cells