A fascinating question of vertebrate development is how a single cell population—the cranial neural crest—creates such different types of structures as the peripheral nervous system and head skeleton. To date, the molecular signals that instruct neural crest cells to develop into head skeleton at the expense of nervous system have remained elusive. One reason why such signals have been difficult to identify is that they may be required at multiple stages of development—such as in the emergence of neural crest cells themselves. In order to overcome this challenge, we developed a transgenic system in zebrafish that allows us to alter signaling precisely at the stage when neural crest cell fates are determined. In so doing, we have found that the early movement of neural crest cells allows them to escape the influence of suppressive signals at their birthplace, which, in turn, sets in motion a cascade that turns off nervous system genes and turns on head skeleton genes. Together, our studies show how the timing of neural crest cell movement plays a major role in biasing early neural crest cells to form the head skeleton.