Acetylcholine and regulation of gene expression in developing systems.

One of the major questions related to nervous system development is the identification of signals directing neuronal populations to specific phenotypes (e.g., cholinergic, adrenergic, or peptidergic neurons) and involved in cell-to-cell interactions. Although neurotrophins have long been known for their function in development, the neurotransmitter role as modulator of gene expression and differentiation has been recognized only recently. Evidence for the ability of various neurotransmitter molecules to influence various cellular events during neuron differentiation has been reported in several systems (Lauder and Schambra, 1999). We have focused our interest on acetylcholine (ACh) and its possible role in the regulation of neuron-specific gene expression, using different experimental systems: (1) neuroblastoma cell lines, as a model of cholinergic neuron differentiation; (2) dorsal root ganglia (DRG) sensory neurons, which activate the expression of a cholinergic system early in development, in spite of their peptidergic or aminoacidergic neurotransmission; and (3) primary cultures of Schwann cells. Data obtained on each system will be described briefly.