Nociceptive sensory neurons derive from contralaterally migrating, fate-restricted neural crest cells.

Neural crest cells (NCCs) are a transient population of multipotent progenitors that give rise to numerous cell types in the embryo. An unresolved issue is the degree to which the fate of NCCs is specified prior to their emigration from the neural tube. In chick embryos, we identified a subpopulation of NCCs that, upon delamination, crossed the dorsal midline to colonize spatially discrete regions of the contralateral dorsal root ganglia (DRG), where they later gave rise to nearly half of the nociceptor sensory neuron population. Our data indicate that before emigration, this NCC subset is phenotypically distinct, with an intrinsic lineage potential that differs from its temporally synchronized, but ipsilaterally migrating, cohort. These findings not only identify a major source of progenitor cells for the pain- and temperature-sensing afferents, but also reveal a previously unknown migratory pathway for sensory-fated NCCs that requires the capacity to cross the embryonic midline.