Neural crest cells (NCCs) are pluripotent cells that emerge from the neural epithelium, migrate extensively, and differentiate into numerous derivatives, including neurons, glial cells and pigment cells. It was initially proposed that the NCCs are naïve, and under the influence of environmental cues that direct their migration and differentiation. However, this is not true for the melanoblasts. First, these cells are fate restricted upon emigration, and secondly, we have shown that only NCCs specified as melanoblasts can migrate dorsolaterally. These observations suggest that early specification dictates their pathway choice. Here, we investigated whether this pathfinding model applies to NCCs more generally by assessing the migration and patterning of the vagal NCCs. First, we performed neural tube serial replating experiments to address their developmental bias. These experiments revealed that the NCCs that first leave the neural tube favor a cardiac fate, whereas the NCCs that leave last favor a melanogenic fate. Neurons and glial differentiate from NCCs that migrate during all time periods. Next, we fluorescently-labeled the vagal NCCs to determine the pathways of migration to specific destinations, including the pharyngeal arches, the heart, the peripheral nervous system (PNS) and the gut. We show that NCCs migrate dorsolaterally to populate the pharyngeal arches and the heart, while most of the neurons and glial cells that populate the gut and generate the PNS migrate ventrally. Finally, we addressed whether the developmental restriction observed in cell culture correlated with pathway choice. When dorsolaterally-migrating NCCs are heterotopically transplanted into stage-matched embryos, they migrate ventrally to populate the peripheral ganglia and the gut, when they normally migrate dorsolaterally to the pharyngeal arches and the heart. This suggests that their migratory behavior is largely dictated by the environment. Conversely, when ventrally-migrating NCCs are heterotopically transplanted into stage-matched embryos, they still migrate ventrally. Thus, these cells behave like trunk NCCs, whose behavior is controlled by lineage restriction. We conclude that migratory differences within the vagal NCCs exist, but that pathway choice is not rigidly specified. Moreover, our data add to the growing notion of the vagal region as a transition zone between the head and the trunk.
|Advisor:||Erickson, Carol A.|
|Commitee:||Rose, Lesilee, Tucker, Richard|
|School:||University of California, Davis|
|Department:||Cell and Developmental Biology|
|School Location:||United States -- California|
|Source:||DAI-B 71/06, Dissertation Abstracts International|
|Keywords:||Cardiac, Circumpharyngeal crest, Enteric, Pathway choice, Prespecification, Vagal neural crest|
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