Regulation by neurotransmitter receptors of serotonergic or catecholaminergic neuronal cell differentiation

The murine FS-derived 1C11 clone exhibits a stable epithelial morphology, e xpresses nestin, an early neuroectodermal marker, and expresses genes invol ved in neuroectodermal cell fate, Upon appropriate induction, 100% of 1C11 precursor cells develop neurite extensions and acquire neuronal markers (N- CAM, synaptophysin, gamma gamma-enolase, and neurofilament) as well as the general functions of either serotonergic (1C11*(/5HT)) (5HT, 5-hydroxytrypt amine) or noradrenergic (1C11**(/NE)) (NE, norepinephrine) neurons. The two programs are shown to be mutually exclusive. 1C11 thus behaves as a neuroe pithelial cell line with a dual bioaminergic fate. 1C11*(/5HT) cells implem ent a functional 5-HT transporter and thereby a complete serotonergic pheno type within a days, whereas 5-HT1B/D, 5-HT2B, and 5-HT2A receptors are sequ entially induced. The accurate time schedule of catecholaminergic different iation was defined. Catecholamine synthesis, storage, and catabolism are ac quired within 4 days; the noradrenergic phenotype is complete at day 12 and includes a functional norepinephrine transporter and an alpha(1D)-adrenore ceptor (day 8). The time-dependent onset of neurotransmitter-associated fun ctions proper to either program is similar to in vivo observations. Along e ach pathway, the selective induction of serotonergic or adrenergic receptor s is shown to be an essential part of the differentiation program, since th ey promote an autoregulation of the corresponding phenotype.