OVEREXPRESSION OF NERVE GROWTH-FACTOR IN SKIN CAUSES PREFERENTIAL INCREASES AMONG INNERVATION TO SPECIFIC SENSORY TARGETS

The impact of increased levels of skin-derived nerve growth factor (NG F) neurotrophin on sensory and sympathetic innervation to the mouse my stacial pad and postero-orbital vibrissae was determined. Consistent w ith an approximate doubling of neuron number in trigeminal and superio r cervical ganglia, many components of the sensory and sympathetic inn ervation were substantially enhanced. Although the increased number of neurons raised the possibility that all types of innervation were inc reased, immunohistochemical analysis indicated that enhanced NGF produ ction had a differential effect upon sensory innervation, primarily in creasing unmyelinated innervation. This increased innervation occurred in specific locations known to be innervated by small, unmyelinated f ibers, suggesting that NGF modulated sensory innervation density, but not targeting. In contrast, sympathetic innervation was not only incre ased but also was distributed to some aberrant locations. In the inter vibrissal for of the mystacial pad, both the number of sensory axons a nd branches appeared increased, whereas in vibrissal follicle sinus co mplexes, only branching increased. In some areas, sensory ending densi ty was lower than expected based upon the size of the source nerve bun dles suggesting that many axons and branches were surviving but failin g to form functional endings. Furthermore, the immunochemical profile of innervation was altered in some sensory populations as demonstrated by the coexistence of RT-97 neurofilament labeling in calcitonin gene -related peptide (CGRP) positive axons, by the loss of substance P col ocalization in some CGRP axons, and by an absence of neuropeptide Y la beling in tyrosine hydroxylase positive sympathetic axone. Collectivel y, these results indicate that the NGF mediated increase in neuron num ber may be selective for particular sets of innervation and that incre ases among some populations may result from phenotypic switching. J. C omp. Neurol. 387:489-506, 1997. (C) 1997 Wiley-Liss, Inc.