Development and neuronal dependence of cutaneous sensory nerve formations: Lessons from neurotrophins

Null mutations of genes from the NGF family of NTs and their receptors (NTRs) lead to loss/reduction of specific neurons in sensory ganglia; conversely, cutaneous overexpression of NTs results in skin hyperinnervation and increase or no changes in the number of sensory neurons innervating the skin. These neuronal changes are paralleled with loss of specific types of sensory nerve formations in the skin. Therefore, mice carrying mutations in NT or NTR genes represent an ideal model to identify the neuronal dependence of each type of cutaneous sensory nerve ending from a concrete subtype of sensory neuron, since the development, maintenance, and structural integrity of sensory nerve formations depend upon sensory neurons. Results obtained from these mouse strains suggest that TrkA positive neurons are connected to intraepithelial nerve fibers and other sensory nerve formations depending from C and Adelta nerve fibers; the neurons expressing TrkB and responding to BDNF and NT-4 innervate Meissner corpuscles, a subpopulation of Merkell cells, some mechanoreceptors of the piloneural complex, and the Ruffini's corpuscles; finally, a subpopulation of neurons, which are responsive to NT-3, support postnatal survival of some intraepithelial nerve fibers and Merkel cells in addition to the muscle mechanoreceptors. On the other hand, changes in NTs and NTRs affect the structure of non-nervous structures of the skin and are at the basis of several cutaneous pathologies. This review is an update about the role of NTs and NTRs in the maintenance of normal cutaneous innervation and maintenance of skin integrity.