Target-derived molecules that influence the development of neurons in the avian ciliary ganglion.

The developing avian ciliary ganglion has been a particularly amenable system for the identification, isolation, and characterization of putative target-derived molecules that mediate retrograde interactions. To date a number of biochemically distinct activities that regulate neuronal survival, transmitter phenotype, and chemosensitivity of ciliary ganglion neurons have been identified. Of these, only two survival-promoting molecules have been purified to homogeneity: ciliary neurotrophic factor and a related molecule, growth-promoting activity. A somatostatin-inducing activity found in cultured choroid cells is very likely to be chick activin A. Other molecules that regulate acetylcholine and acetylcholine receptor expression comigrate on a gel filtration column at a molecular weight of 50-60 kD, but they have yet to be isolated. Once molecules that mimic retrograde influences are identified, a number of criteria must be met before their physiological significance can be established. These criteria are (1) availability of the molecule from the target at the appropriate time in development; (2) ability of the neurons to respond to the molecule at the appropriate time in development; (3) demonstration that blocking the activity or availability of the molecule is able to block the target-derived developmental change expressed in the neurons. Of the molecules that are thought to retrogradely influence ciliary neuron development, only growth-promoting activity is known to meet criteria 1 and 2, and experiments are currently underway to test whether inhibition of growth-promoting activity in vivo will exacerbate normal cell death.