Overexpression of neurotrophin 4 in skin enhances myelinated sensory endings but does not influence sensory neuron number.

The growth factors neurotrophin 4 (NT4) and brain-derived neurotrophic factor (BDNF) are expressed in the developing skin, activate the trkB tyrosine kinase receptor, and influence the development and survival of specific types of sensory afferents. Whether each factor is capable of regulating the same or overlapping populations of cutaneous afferents during development is unknown. A previous study of mice overexpressing BDNF in the developing skin (BDNF-OE mice) revealed that these animals exhibited increased hair follicle innervation, Meissner corpuscle size, and Merkel cell number in glabrous skin, although no change in the total number of sensory neurons was observed. To determine if NT4 affects cutaneous innervation in a manner similar to BDNF, transgenic mice overexpressing NT4 in skin, under the control of the keratin 14 gene promoter, were examined. Similar to BDNF-OE mice, NT4-OE mice had increased innervation to the skin but no increase in sensory neuron number in either the dorsal root ganglion or trigeminal ganglion. NT4 overexpression also enhanced hair follicle innervation and the size and density of innervation to Meissner corpuscles. Unlike BDNF overexpression, NT4 overexpression did not alter the number of Merkel cells in the glabrous skin, but it did enhance the number of myelinated axons in nerves projecting to skin. Thus, the same pattern of BDNF and NT4 overexpression within the skin produces phenotypes that are both similar and distinctive.