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.