NT3 expressed in skin causes enhancement of SA1 sensory neurons that leads to postnatal enhancement of Merkel cells

To determine the role of NT3 in the postnatal maturation of Merkel cell (MC) sensory neurite complexes (touch domes), we examined the development of their neural and end-organ components in wild-type and transgenic mice that overexpress NT3 (NT3-OE). Touch domes are sensory complexes of the skin that contain specialized MCs innervated by slowly adapting type 1 (SA1) neurons. Touch domes are dependent on NT3 and, though formed in newborn mice that lack NT3, are severely depleted during postnatal maturation. Mice that overexpress NT3 in the skin have larger touch domes characterized by enhanced neural innervation and MC number. In this study, we asked how this NT3-mediated enhancement occurs, whether through stimulatory effects of NT3 on the SA1 neuron, or the MC, or both. The innervation density and number of MCs associated with each touch dome were measured in wild-type and transgenic animals at postnatal times. In newborn NT3-OE mice, touch dome innervation was enhanced. Surprisingly, however, the number of MCs was lower in newborn NT3-OE animals than in wild-type litter-mates, and equivalent numbers were not reached until postnatal day 8 (PN8). Not until the PN12 and PN16 time points did MCs increase in NT3-OE mice. To examine the neural dependence of MCs in NT3-OE mice, touch domes were chronically denervated by resecting dorsal cutaneous nerves. Both wild-type and NT3-OE animals showed similar depletion in the number of MCs associated with touch domes. These data indicate that NT3 is not a survival factor for MCs and that the NT3-mediated enhancement of MC number is indirect and neurally dependent. (C) 2004 Wiley-Liss, Inc.