Cutaneous overexpression of NT-3 increases sensory and sympathetic neuron number and enhances touch dome and hair follicle innervation.
Target-derived influences of nerve growth factor on neuronal survival and differentiation are well documented, though effects of other neurotrophins are less clear. To examine the influence of NT-3 neurotrophin overexpression in a target tissue of sensory and sympathetic neurons, transgenic mice were isolated that overexpress NT-3 in the epidermis. Overexpression of NT-3 led to a 42% increase in the number of dorsal root ganglia sensory neurons, a 70% increase in the number of trigeminal sensory neurons, and a 32% increase in sympathetic neurons. Elevated NT-3 also caused enlargement of touch dome mechanoreceptor units, sensory end organs innervated by slowly adapting type 1 (SA1) neurons. The enlarged touch dome units of the transgenics had an increased number of associated Merkel cells, cells at which SA1s terminate. An additional alteration of skin innervation in NT-3 transgenics was an increased density of myelinated circular endings associated with the piloneural complex. The enhancement of innervation to the skin was accompanied by a doubling in the number of sensory neurons expressing trkC. In addition, measures of nerve fibers in cross-sectional profiles of cutaneous saphenous nerves of transgenics showed a 60% increase in myelinated fibers. These results indicate that in vivo overexpression of NT-3 by the epidermis enhances the number of sensory and sympathetic neurons and the development of selected sensory endings of the skin.
Albers
K M
KM
Department of Pathology, University of Kentucky Medical Center, Lexington 40536, USA. kmalbe00@pop.uky.edu
Perrone
T N
TN
Goodness
T P
TP
Jones
M E
ME
Green
M A
MA
Davis
B M
BM
D000818:Animals; D001369:Axons / Q000502:physiology; D001483:Base Sequence; D002452:Cell Count; D018076:DNA, Complementary; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000648:ultrastructure; D015870:Gene Expression; D018859:Hair Follicle / Q000294:innervation*; D008465:Mechanoreceptors / Q000502:physiology*; D018862:Merkel Cells / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology* / Q000648:ultrastructure; D020933:Neurotrophin 3; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D012867:Skin / Q000294:innervation
D018076:DNA, Complementary; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC