The effect of target and non-target elements on the survival of chick ciliary ganglion neurons {\it in vitro\/}

Developing neurons of the peripheral nervous system undergo a period of cell death during which up to 80% of the neurons born during the proliferative phase die. This work was undertaken to test the general hypothesis that target tissues support the survival of the neurons that innervate them during development. While it is well known that striated muscle targets support neuronal survival, little is known about the role of smooth muscle targets on the survival of their innervating neurons. This principle was tested in a smooth muscle target system by Creedon and Tuttle (1988). They demonstrated that the smooth muscle target organ of the avian ciliary ganglion lacked the ability to support ciliary ganglion neurons in vitro and suggested the intriguing possibility that survival is regulated differently in neurons innervating smooth muscle and striated muscle targets. In vitro studies are described herein that refute this finding and demonstrate that this target acts much the same way as do striated muscle targets--that is ciliary ganglion neurons plated on explants of the tissue survive and grow vigorously forming contacts between axons and target cells. Although innervated by a discrete population of ganglionic neurons, no evidence for selective survival of the neurons was found.^ Neuronal survival factors have been purified and characterized on the basis of their ability to support neurons in vitro. Conditioned medium from the choroid (CCM), Ciliary Neuron Trophic Factor (CNTF), and Growth Promoting Activity (GPA) all support the survival of neurons from dissociated ganglia in vitro. CIPE, an aqueous extract of the targets of the ganglion also promotes the survival of the neurons. However, when ganglionic non-neuronal cells were absent, CNTF, CCM and GPA failed to support the neurons. Only the CIPE extract was able to support purified neurons for the entire culture period. Experiments are described that suggest that the factor(s) provided by the non-neuronal cells is comprised of membrane-bound and soluble components and that, in some systems, the combinatorial actions between neurons and NNCs are required for trophic factor-mediated neuronal survival.