Neural mechanisms of hair growth control

Clinical and experimental observations have long suggested that skin nerves have "trophic" functions in hair follicle development, growth and/or cycling, even though the molecular and cellular basis of the underlying neuroepithelial interactions has remained obscure. Here, we critically review currently available evidence arguing in favor of or against the existence of neural mechanisms of hair growth control, and outline why the murine hair cycle provides an excellent experimental system for characterizing and manipulating piloneural interactions. Summarizing relevant, recent data from the C57BL/6 mouse model, it is pointed out that the sensory and autonomic innervation of normal pelage hair follicles, the substance P skin content, and cutaneous mast cell-nerve contacts show striking changes during synchronized hair follicle cycling. Furthermore, the murine hair follicle appears to be both a source and a target of neurotrophins, whereas neuropharmacologic manipulations alter murine hair follicle cycling in vivo. For example, anagen is induced by substance P or adrenocorticotropin (ACTH), and by the experimentally triggered release of neuropeptides from sensory nerves and of neurotransmitters from adrenergic nerves. Taken together, this argues in favor of neuroepithelial interactions as regulatory elements in hair growth control and suggests that the study of piloneural interactions promises important insights into general principles of neuroepithelial communication, namely during epithelial morphogenesis and remodeling. We delineate a hypothetical working model of piloneural interactions and propose that targeted manipulations deserve systematic exploration as a novel strategy for managing hair growth disorders.