The Differentiation of the Neurotransmitter Phenotypes in Chick Sympathetic Neurons

Abstract

In this chapter the identification of cell interactions involved in the induction of a specific neurotransmitter phenotype and characterization of the growth factors that are mediating these inductive interactions have been summarized. The analysis of the noradrenergic differentiation of postganglionic sympathetic neurons has been accelerated by the availability of markers indicating catecholamine biosynthesis and storage in embryonic tissue. In the chick embryo, tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, is expressed after the neural crest-derived precursors of the sympathetic neurons have gathered at the dorsal aorta to form the primary sympathetic ganglia. In addition to the dorsal aorta, several embryonic tissues have been demonstrated to promote catecholaminergic differentiation in developing sympathetic neurons or their precursors. In particular, ventral neural tube and notochord are necessary for catecholaminergic differentiation of sympathetic neurons in vivo . The search of identified growth factors that mediate the induction of noradrenergic differentiation in sympathetic neurons revealed that bone morphogenetic proteins (BMPs) are effective in inducing TH expression in vitro and in vivo . This observation indicates that BMPs are able to promote catecholaminergic differentiation in neural crest-derived sympathetic precursors in vitro as well as in vivo . Significantly, BMP-4 and -7 are expressed in the dorsal aorta before and during noradrenergic differentiation of sympathetic neurons. Markers of the cholinergic neurotransmitter phenotype, such as the enzymes choline acetyltransferase (CHAT), acetylcholine esterase (AChE), and the neuropeptide vasoactive intestinal peptide (VIP), are detectable only after sweat gland innervation. Whereas BMPs have been shown to be prime candidates for the growth factors mediating the induction of noradrenergic differentiation of sympathetic neurons in the primary sympathetic ganglia, the factors responsible for the induction of CHAT expression are unknown.