Relation of target encounter and neuronal death to nerve growth factor responsiveness in the developing mouse...

An aim of this study was to define precisely the period in the developmental history of primary sensory neurons during which nerve growth factor (NGF) exerts its growth-promoting effect. The mouse trigeminal ganglion and its peripheral projection were studied at closely staged intervals throughout development using light and electron microscopy, and the influence of NGF and anti-NGF antiserum on neurite outgrowth from ganglion explants was investigated at corresponding stages in culture. By embryonic day 9.5 (E9.5) peripheral fibers were first visible and increased in number until E13. Throughout this period in vitro neurites grew in the presence of anti-NGF. Peripheral fibers initially contacted the epithelium of the mandibular process by E10.5 and the maxillary process by E11. This coincided with the stage in vitro during which the magnitude of neurite outgrowth was significantly increased by NGF. The development of this response was independent of target encounter since it occurred in neurons which had not contacted their targets prior to explantation. There was an approximate one-to-one relationship between the number of neurons in the ganglion and peripheral fibers throughout development. A peak of some 44,400 fibers and 42,600 neurons was reached by E13 and fell to 20,800 and 19,000, respectively, by birth. Neurite outgrowth was elicited by NGF throughout the period of neuronal death. It is argued that the time course of the influence of NGF is consistent with a role as a selective maintenance factor but not as an agent directing initial outgrowth.