The long term objective of these studies is to understand how NT3 influences sensory receptor organ development and innervation. NT3 affects proliferation and survival of both neuronal and nonneuronal cells during development and mediates communication between sensory end organs and neurons. This proposal will focus on a sensory mechanoreceptor, the touch dome-Merkel cell-neurite complex, because NT3 overexpression in skin has been shown to increase touch dome size, innervation and numbers of associated Merkel cells (Albers et al., 1996). The studies of this proposal will 1) determine the importance of NT3 derived only from skin on touch dome formation and innervation, 2) determine the role, if any, innervation has on mediating the receptor organ enlargement seen with NT3 overexpression, 3) determine the developmental time course for NT3 mediated enlargement of receptor end organs, and 4) determine what neurotrophin receptors are expressed in touch domes during that time. These studies are the first step to identify the mechanisms which underlie changes induced by NT3 in the skin-derived sensory targets of neurons. Future studies will attempt to identify (using representational difference analysis; RDA) genes expressed in both the target and neuron that temporally regulate development of touch dome end organs. By examining how NT3 acts on a sensory receptor organ, the mechanisms by which NT3 acts on both neuronal and nonneuronal cell types in the same system and how NT3 could be involved in the communication between these two cell types during development will begin to be uncovered. From a clinical perspective, NT3 may act via similar mechanisms to reestablish and maintain sensory receptor end organs after nerve damage or in skin grafts.
| Krimm, R F; Miller, K K; Kitzman, P H et al. (2001) Epithelial overexpression of BDNF or NT4 disrupts targeting of taste neurons that innervate the anterior tongue. Dev Biol 232:508-21 |
| Krimm, R F; Davis, B M; Albers, K M (2000) Cutaneous overexpression of neurotrophin-3 (NT3) selectively restores sensory innervation in NT3 gene knockout mice. J Neurobiol 43:40-9 |
