Integration of whole-body single-cell transcriptomics with electron microscopy volume in the marine annelid Platynereis dumerilii reveals that 173 individuated cell types are organized by large differentiation coregulons implementing eight major cellular morphotypes, and identifies 14 neuronal families defined by conserved transcription factor combinations that match vertebrate, insect, and nematode neuron types by molecular signature, axonal projection, and sensory apparatus, supporting their existence in urbilaterian ancestors as the ancient core of nervous system centralization.

Differential gene expression establishes the distinct physiology and morphology of cell types in an animal body. Single-cell sequencing and volume EM represent milestones toward the characterization of cell types, yet are difficult to combine for a comprehensive view on the cellular genotype-phenotype link. Here, we map a whole-body single-cell transcriptome into the PlatyBrowser, a multimodal cellular atlas for the marine annelid Platynereis dumerilii, and establish this combination uniquely for an entire animal. We learn that, in the 6-days-old worm, the majority of genes are tightly co-regulated to jointly implement one of eight major cellular morphotypes representing epidermis, gut, vasculature, myofibres, glia, motile cilia, glands, or neurons. Focusing on neurons, we uncover 14 families that by transcription factor identity, axonal projection, or sensory-secretory apparatus resemble conserved neuron types found in vertebrates, insects, or nematodes. We hypothesize that these existed in urbilaterian ancestors and represent the ancient core of nervous system centralization.