Regulation of the neural crest cell fate by N-myc: promotion of ventral migration and neuronal differentiation.

During neural crest development in avian embryos, transcription factor N-myc is initially expressed in the entire cell population. The expression is then turned off in the period following colonization in ganglion and nerve cord areas except for the cells undergoing neuronal differentiation. This was also recapitulated in the culture of Japanese quail neural crest, and the cells expressing N-myc eventually coincided with those expressing neurofilaments. These findings suggested that N-myc is involved in regulation of neuronal differentiation in the neural crest cell population. In fact, transient overexpression of N-myc in the neural crest culture by transfection resulted in a remarkable promotion of neuronal differentiation. An experimental procedure was developed to examine the effect of exogenous N-myc expression in the neural crest cells in embryos. Neural crest cell clusters still attached to the neural tube were excised from Japanese quail embryos, transfected and grafted into chicken host embryos. Using this chimera technique, we were able to analyze the consequence of transient high N-myc during the early phase of neural crest migration. Two effects were demonstrated in the embryos: first, high N-myc expression provoked massive ventral migration of the neural crest population and, second, those cells that migrated to the ganglion-forming areas underwent neuronal differentiation with the cell type determined by the nature of the ganglion. Thus, N-myc is involved in regulation of the neural crest fate in two different aspects: ventral migration and neuronal differentiation.