Lineage-specific elaboration of a conserved cnidogenic program drives cnidocyte diversification and illuminates cell type evolution.

Cnidocytes are a cnidarian synapomorphy that diversified considerably across the phylum, making them an excellent model to investigate how novel cell types emerge and evolve. By investigating the regulatory program patterning cnidocytes in the sea anemone Nematostella vectensis, we identified at least six molecular pathways contributing to the cnidogenic gene regulatory network, including a novel lineage-restricted transcription factor, NvfoxE-like, whose expression and targets are exclusive to cnidocytes. While Nvznf845 and NvpaxA represent a conserved pan-cnidarian core program, NvfoxE-like and other lineage-specific genes represent elaborations restricted to hexacorallians or Nematostella specifically. Comparative analysis across cnidarian lineages reveals that only ~25% of cnidocyte-expressed genes are broadly conserved, while ~40% lack clear homologs outside Nematostella, consistent with substantial lineage-specific cnidogenic transcriptional profiles. While all cnidocytes have the same basic blueprint, there is extensive variation in harpoon morphology, venom composition, and capsule opening mechanisms. This suggests that rapid diversification of cnidocyte development occurred as new lineages arose. Our findings suggest that homologous cell types can share less than 25% transcriptional similarity, and perhaps less for more ancient cells, providing a molecular framework for understanding cell type diversification across evolution.