GROWTH-FACTOR ACTION IN NEURAL CREST CELL DIVERSIFICATION

At the onset of their migration into the embryo, many neural crest cel ls are pluripotent in the sense that they have the capacity to generat e progeny that consist of more than one cell type. More recently, we h ave found that there are pluripotent neural crest cell-derived cells e ven at sites of terminal differentiation. These findings support the n otion that cues originating from the microenvironment, at least in par t, direct neural crest cell type specification. Based on the rationale that growth factors that are known to support survival of neural cres t cell derivatives may have additional functions in progenitor cell de velopment, we have examined the action of pertinent growth factors. Tr ophic, mitogenic, antiproliferative and differentiation promoting acti vities were found. Stem cell factor (SCF) is trophic for pluripotent n eural crest cells. Contrary to expectation, SCF plus a neurotrophin, r ather than SCF alone, is trophic for committed melanogenic cells. Basi c fibroblast growth factor (bFGF) is mitogenic both for pluripotent ce lls and committed melanogenic cells. However, the cells become depende nt on another factor for survival. Whereas any neurotrophin tested can rescue bFGF-activated pluripotent neural crest cells, the factor that rescues melanogenic cells remains to be determined. Transforming grow th factor beta 1 (TGF-beta 1) is a powerful antimitotic signal for all neural crest cells that overrides the bFGF/neurotrophin proliferative signal. Furthermore, SCF promotes differentiation of neural crest cel ls into cells of the sensory neuron lineage. Neurotrophin-3 (NT-3) spe cifically promotes high affinity uptake of norepinephrine by neural cr est cells and is thus thought to play a critical role in the different iation of sympathetic neuroblasts. In summary, our data indicate that neurotrophins and other pertinent growth factors affect survival, prol iferation and differentiation of neural crest cells at multiple levels and in different lineages. Moreover, our findings emphasise the impor tance of the concerted action of combinations of growth factors, rathe r than of individual factors.