Development of the nervous system is dependent on the co-operation between
cell determination events and the action of epigenetic factors; in addition
to well known factors, e.g. growth factors, neurotransmitters have been as
signed a role as "morphogens" and modulators of neuronal differentiation in
an early developmental phase. The possible role of acetylcholine as a modu
lator of neuronal differentiation has been considered in two experimental s
ystems. A neuroblastoma cell line, which does not synthesise any neurotrans
mitter, has been transfected with a choline acetyltransferase construct; ac
tivation of acetylcholine synthesis, thus achieved, is followed by a higher
expression of neuronal specific traits. The presence in these cells of mus
carinic receptors is consistent with the existence of an autocrine loop, wh
ich may be responsible for the more advanced differentiation state observed
in the transfected cells. Expression of cholinergic markers appears as a c
ommon feature of DRG sensory neurons, independently of the neurotransmitter
used. Choline acetyltransferase can be detected in DRG at early developmen
tal stages. The distribution of muscarinic receptors in DRG has suggested t
hat activation of acetylcholine synthesis may be related in an early develo
pmental phase to the interaction between neurons and nonneuronal cells and
to modulation of cell differentiation. Both systems suggest that acetylchol
ine may have a role as a modulator of neuronal differentiation.