Journal: Nature
This study investigates when and how neural crest cells (NCCs) commit to specific fates, and how individual progenitors contribute to different neural crest derivatives.
Using CRISPR-based barcoding in mice and analysis of naturally occurring mosaic variants in humans, the authors track clonal relationships among neural crest descendants. They find:
- Neural crest progenitor clones spread extensively along the rostrocaudal axis and bilaterally, indicating wide spatial dispersion of individual progenitors.
- Despite this broad spread, there is limited clonal overlap between sensory and sympathetic lineages, suggesting these lineages largely arise from distinct, fate-restricted progenitor pools.
- Computational modeling of the mosaic-variant data supports that most NCCs become strongly fate-restricted before they delaminate from the neural tube, rather than remaining broadly multipotent at the time of migration.
- Live imaging in quail embryos shows fibroblast growth factor (FGF)-dependent rostrocaudal dispersion of NCCs, indicating a signaling mechanism that promotes their axial spread across multiple levels.
Overall, the work supports a model in which neural crest fate bias is established primarily within the neural tube, with only a minority of delaminated cells retaining multipotency to generate both sensory and sympathetic derivatives.