Evolution of synapses and neurotransmitter systems: The divide-and-conquer model for early neural cell-type evolution

Nervous systems evolved around 560 million years ago to coordinate and empower animal bodies. Ctenophores - one of the earliest-branching lineages - are thought to share a few neuronal genes with bilaterians and may have evolved neurons convergently. Here we review our current understanding of the evolution of neuronal molecules in nonbilaterians. We also reanalyse single-cell sequencing data in light of new cell-cluster identities from a ctenophore and uncover evidence supporting the homology of one ctenophore neuron-type with neurons in Bilateria. The specific coexpression of the presynaptic proteins Unc13 and RIM with voltage-gated channels, neuropeptides and homeobox genes pinpoint a spiking sensory-peptidergic cell in the ctenophore mouth. Similar Unc13-RIM neurons may have been present in the first eumetazoans to rise to dominance only in stem Bilateria. We hypothesise that the Unc13-RIM lineage ancestrally innervated the mouth and conquered other parts of the body with the rise of macrophagy and predation during the Cambrian explosion.