Unique homeobox codes delineate all the neuron classes of C. elegans

It is not known at present whether neuronal cell-type diversity—defined by cell-type-specific anatomical, biophysical, functional and molecular signatures—can be reduced to relatively simple molecular descriptors of neuronal identity¹. Here we show, through examination of the expression of all of the conserved homeodomain proteins encoded by the Caenorhabditis elegans genome², that the complete set of 118 neuron classes of C. elegans can be described individually by unique combinations of the expression of homeodomain proteins, thereby providing—to our knowledge—the simplest currently known descriptor of neuronal diversity. Computational and genetic loss-of-function analyses corroborate the notion that homeodomain proteins not only provide unique descriptors of neuron type, but also have a critical role in specifying neuronal identity. We speculate that the pervasive use of homeobox genes in defining unique neuronal identities reflects the evolutionary history of neuronal cell-type specification.