The peripheral nervous system (PNS) is derived from a transitory embryonic structure, the neural crest with an additional contribution of the cephalic ectodermal placodes to the sensory ganglia of certain cranial nerves. In vivo grafting experiments, taking advantage of the quail/chick marker system, allowed the fate map of the neural crest to be constructed and the precise level of origin along the neuraxis of the component cells of PNS ganglia to be defined. It appeared that the neural crest is regionalized in different areas from which a limited number of phenotypes arise. However, if the position of neural crest fragments is experimentally changed prior to the onset of migration, it turns out that virtually all the cell types represented in PNS ganglia can arise from any level of the neural crest, provided it is transplanted into the appropriate level of the neuraxis. This means that the microenvironment into which the neural crest cells migrate plays a critical role in directing their differentiation. Further in vivo studies along with in vitro clonal analysis of neural crest developmental potencies revealed that, during the migratory phase, the crest cells are already highly heterogeneous in their state of commitment. When they reach the sites of gangliogenesis, they exhibit different requirements for growth and differentiation. Our current studies are aimed at identifying the factors that, in spinal and sympathetic ganglia respectively, trigger the differentiation of sensory and adrenergic sympathetic neurons. The brain-derived neurotrophic factor (BDNF) and insulin (and/or IGF1) have been shown to play a role in these processes.