Excess target-derived neurotrophin-3 alters the segmental innervation of the skin

It is thought that dermatomes are established during development as a resul t of competition between afferents of neighbouring segments. Mice that over express neurotrophins in the skin provide an interesting model to test this hypothesis, as they possess increased numbers of sensory neurons, and disp lay hyperinnervation of the skin. When dermatomal boundaries were mapped in adult mice, it was found that those in nerve growth factor and brain-deriv ed neurotrophic factor overexpressers were indistinguishable from wild-type animals but that overlap between adjacent segments was greatly reduced in neurotrophin-3 (NT-3) overexpressers. However, dermatomes in heterozygous N T-3 knockout mice displayed no more overlap than wild-types. In order to qu antify differences across strains, innervation territories of thoracic dors al cutaneous nerves were mapped and measured in adult mice. Overlap between adjacent dorsal cutaneous nerves was normal in nerve growth factor overexp ressing mice, but much reduced in NT-3 overexpressers. However, this restri ction was not reflected in the central projection of the dorsal cutaneous n erve, creating a mismatch between peripheral and central projections. Dorsa l cutaneous nerve territories were also mapped in neonatal mice aged postna tal day 7-8. In neonates, nerve territories of NT-3 overexpressers overlapp ed less than wild-types, but in neonates of both strains the amount of over lap was much greater than in the adult. These results indicate that substan tial separation of dermatomes occurs postnatally, and that excess NT-3 enha nces this process, resulting in more restricted dermatomes. It may exert it s effects either by enhancing competition, or by direct effects on the stab ility and formation of sensory endings in the skin.