Neurobiology of the murine pelage hair follicle

Exploitation of the murine pelage hair follicle as a model system that allows one to dissect and experimentally manipulate cutaneous neurobiology has generated a plethora of new insights into the roles of neuropeptides and neurotransmitters in the growth control of epithelial appendages in situ. Cross talk between epithelial-mesenchymal and neuronal cutaneous elements begins with the first development of skin and skin appendages. Development of cutaneous innervation of murine back skin hair follicles follows a strictly regulated spatio-temporal pattern. Cutaneous neural networks contain, e.g., neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P (SP) in distinct distribution patterns. Compared to nontylotrich pelage hair follicles, tylotrich pelage hair follicles receive denser innervation and develop a lateral disc consisting of Merkel cells and SP-immunoreactive nerve fibers. Analysis of murine back skin innervation during the hair cycle has challenged the dogma that peripheral innervation only changes under pathological conditions such as injury. Most intriguingly, during anagen-development in murine back skin, SP-immunoreactive nerve fiber numbers fluctuate profoundly and transiently. Moreover, these fluctuations in nerve fiber numbers are accompanied by fluctuations in mast cell-nerve fiber contacts and in Merkel cell numbers. In organ-cultured early anagen back skin treated with SP, anagen progression can be promoted. These striking, hair cycle-dependent fluctuations in cutaneous innervation suggest trophic properties of piloneural interactions during hair cycle-associated skin remodeling and offer attractive, yet hitherto underexplored new targets for pharmacological intervention in the management of hair growth disorders.