Sponge genes provide new insight into the evolutionary origin of the neurogenic circuit.

The nerve cell is a eumetazoan (cnidarians and bilaterians) synapomorphy [1]; this cell type is absent in sponges, a more ancient phyletic lineage. Here, we demonstrate that despite lacking neurons, the sponge Amphimedon queenslandica expresses the Notch-Delta signaling system and a proneural basic helix loop helix (bHLH) gene in a manner that resembles the conserved molecular mechanisms of primary neurogenesis in bilaterians. During Amphimedon development, a field of subepithelial cells expresses the Notch receptor, its ligand Delta, and a sponge bHLH gene, AmqbHLH1. Cells that migrate out of this field express AmqDelta1 and give rise to putative sensory cells that populate the larval epithelium. Phylogenetic analysis suggests that AmqbHLH1 is descendent from a single ancestral bHLH gene that later duplicated to produce the atonal/neurogenin-related bHLH gene families, which include most bilaterian proneural genes [2]. By way of functional studies in Xenopus and Drosophila, we demonstrate that AmqbHLH1 has a strong proneural activity in both species with properties displayed by both neurogenin and atonal genes. From these results, we infer that the bilaterian neurogenic circuit, comprising proneural atonal-related bHLH genes coupled with Notch-Delta signaling, was functional in the very first metazoans and was used to generate an ancient sensory cell type.