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.
Hoyle
G W
GW
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Mercer
E H
EH
Palmiter
R D
RD
Brinster
R L
RL
D000311:Adrenal Glands / Q000294:innervation; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005727:Ganglia, Spinal / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D010179:Pancreas / Q000294:innervation; D011401:Promoter Regions, Genetic; D013363:Submandibular Gland / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D046911:Macromolecular Substances; D009414:Nerve Growth Factors; D004299:Dopamine beta-Hydroxylase