Neural crest stem cells undergo cell-intrinsic developmental changes in sensitivity to instructive differentiation signals

Rat neural crest stem cells (NCSCs) prospectively isolated from uncultured E14.5 sciatic nerve and transplanted into chick embryos generate fewer neur ons than do NCSCs isolated from E10.5 neural tube explants. In addition, th ey differentiate primarily to cholinergic parasympathetic neurons, although in culture they can also generate noradrenergic sympathetic neurons. This in vivo behavior can be explained, at least in part, by a reduced sensitivi ty of sciatic nerve-derived NCSCs to the neurogenic signal BMP2 and by the observation that cholinergic neurons differentiate at a lower BMP2 concentr ation than do noradrenergic neurons in vitro. These results demonstrate tha t neural stem cells can undergo cell-intrinsic changes in their sensitivity to instructive signals, while maintaining multipotency and self-renewal ca pacity. They also suggest that the choice between sympathetic and parasympa thetic fates may be determined by the local concentration of BMP2.