The long term objective of these studies is to understand how NT3 influences sensory receptor end organ development and innervation. NT3 affects proliferation and survival of both neural and nonneural 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 increases touch dome size and number of associated Merkel cells between postnatal days 12 and 16. The studies of this proposal will focus on this developmental period to 1) determine if increased innervation to individual touch domes precedes increases in Merkel cell number 2) determine if the action of NT3 on the neural innervation of touch domes is the result of increased trkC expression by these neurons. 3) determine if there is a postnatal critical period for the action of NT3 on touch dome development. By examining how NT3 acts on a sensory receptor organ, the mechanisms by which NT3 acts on both neuronal and nonneuronal cells and how NT3 may mediate communication between these two cell types during development will begin to be uncovered. Elucidating how neurotrophins affect sensory end organs has important implications for use of these growth factors as therapeutic agents to enhance sensory regeneration following nerve injury or in disease states that cause sensory degeneration, e.g., diabetic neuropathies.
| 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 |
