Distinct roles for nerve growth factor and brain-derived neurotrophic factor in controlling the rate of hair follicle morphogenesis

Increasing evidence suggests that neurotrophins play an important part in the control of the development of ectodermal derivatives, such as the hair follicle. Here, we show that, during hair follicle morphogenesis in C57BL/6 mice, nerve growth factor, brain-derived neurotrophic factor and their corresponding high-affinity tyrosine kinase receptors, TrkA and TrkB, show stringently controlled spatiotemporal expression patterns in the follicular epithelium and mesenchyme. Constitutive overexpression of nerve growth factor in mice is associated with a discrete, but significant acceleration of hair follicle morphogenesis, whereas this is not seen in brain-derived neurotrophic factor transgenic mice. In neonatal skin organ culture, nerve growth factor and brain-derived neurotrophic factor differentially influence hair follicle development: nerve growth factor accelerates late stages of hair follicle morphogenesis, whereas brain-derived neurotrophic factor does not show significant effects. This suggests that the morphogenetic properties of locally generated neurotrophins in the skin, similar to their classical neurotrophic functions, are quite distinct and depend on the response patterns of the corresponding neurotrophin target receptor-expressing cells in the developing hair follicle. These data further strengthen the concept that neurotrophin signaling is an important element in controlling the rate of hair follicle morphogenesis, yet also highlight the complexity of this signaling system.