EFFECT OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I ON THE EXPRESSION OF THE CATECHOLAMINERGIC PHENOTYPE BY NEURAL CREST CELLS

Neural crest-derived catecholaminergic precursors have been used as a model to study the role of signals supplied by the environment during avian neurogenesis. A new culture system consisting of dissociated sclerotomes or somites isolated at embryonic day 3 (E3) or 2.5 (E2.5) has been established, which allows quantitative comparison of various culture conditions. As a first step of this study, the role of insulin and insulin-like growth factor I (IGF-I) in catecholaminergic differentiation has been investigated. Our results show that both factors are able to increase by a factor 2 to 3 the number of catecholaminergic cells present in the culture of sclerotomes after 24 h of culture. The effect is dose-dependent and the half-maximal effect is obtained with low concentrations of each peptide. Since insulin, IGF-I and their respective receptors are present at this stage of development in avian embryo, our observations suggest that an early step in catecholaminergic differentiation could be under at least the partial control of insulin and insulin-related peptides. On the other hand, neural crest precursors isolated at E2.5 are not able to generate catecholaminergic cells and to respond to insulin when cultivated for one day, indicating that these precursors are subjected in vivo to a maturation step, within the somite/sclerotome between E2.5 and E3; this step could be obtained in vitro by cultivating the precursors for 1 day, which resulted in the development of insulin responsiveness by catecholaminergic precursors.