EXPRESSION OF NGF IN SYMPATHETIC NEURONS LEADS TO EXCESSIVE AXON OUTGROWTH FROM GANGLIA BUT DECREASED TERMINAL INNERVATION WITHIN TISSUES

The effects of nerve growth factor (NGF) on sympathetic axon growth were investigated by generating transgenic mice in which the beta subunit of NGF was expressed in sympathetic neurons using the human dopamine beta-hydroxylase (DBH) promoter. In DBH-NGF mice, the sympathetic trunk and nerves growing to peripheral tissues were enlarged and contained an increased number of sympathetic fibers. Although sympathetic axons reached peripheral tissues, terminal sympathetic innervation within tissues was decreased in DBH-NGF mice. This effect could be reversed in the pancreas by overexpression of NGF in pancreatic islets. The observations are consistent with a model in which NGF gradients are not required to guide sympathetic axons to their targets, but are required for the establishment of the normal density and pattern of sympathetic innervation within target tissues.