ABSTRACT

The role of neurotransmitter molecules as modulators of early developmental events has received consistent experimental support in a number of different systems. We have investigated the role of acetylcholine in neuron differentiation as modulator of neurospecific gene expression. This problem was approached using two experimental models: developing sensory neurons of chick dorsal root ganglia and mouse neuroblastoma stable lines. As far as dorsal root ganglia are concerned is well known that their neurotrasmission apparatus is made of neuropeptides and aminoacids; however we have shown that at a very early stage they express a functional cholinergic system (including biosynthetic and inactivating enzymes and muscarinic and nicotinic receptor system), which has been suggested to be responsible for the modulation of genes involved in neuron differentiation (e.g. neurofilament components) and possibly for neuron-glia crosstalk. On the other hand transfection of neurotransmitter inactive neuroblastoma cells with a choline acetyltransferase construct has been shown to activate the expression of neurospecific genes, either upregulating those expressed at a low level or activating silent ones. It has thus been proposed that in this system an autoregulatory loop is activated, which may be active in the embryos. The data obtained in the two systems point to a role for acetylcholine among epigenetic factors acting on gene expression regulation in early stage of development.