Genomic mosaicism reveals developmental organization of trunk neural crest-derived ganglia

The neural crest generates numerous cell types, but conflicting results leave developmental origins unresolved. Here using somatic mosaic variants as cellular barcodes, we infer embryonic clonal dynamics of trunk neural crest, focusing on the sensory and sympathetic ganglia. From three independent adult neurotypical human donors, we identified 1,278 mosaic variants using deep whole-genome sequencing, then profiled allelic fractions in 187 anatomically dissected ganglia. We found a massive rostrocaudal spread of progenitor clones specific to sensory or sympathetic ganglia, which unlike in the brain, showed robust bilateral distributions. Computational modeling suggested neural crest progenitor fate specification preceded delamination from neural tube. Single-cell multiomic analysis suggested both neurons and glia contributed to the rostrocaudal clonal organization. CRISPR barcoding in mice and live imaging in quail embryos confirmed these clonal dynamics across multiple somite levels. Our findings reveal an evolutionarily conserved clonal spread of cells populating peripheral neural ganglia. Highlights- Genetic mosaicism and real-time imaging reveal trunk neural crest cellular dynamics. - DRG or SG cells from different axial levels are more lineage-related than from the same level. - Cell fate specification of trunk neural crest progenitors occurs before neural tube delamination. - These aspects of clonal organization are evolutionarily conserved across mammals and avians.