In silico analysis of the transcriptional regulatory logic of neuronal identity specification throughout the <i>C. elegans</i> nervous system.

Abstract

The generation of the enormous diversity of neuronal cell types in a differentiating nervous system entails the activation of neuron type-specific gene batteries. To examine the regulatory logic that controls the expression of neuron type-specific gene batteries, we interrogate single cell expression profiles of all 118 neuron classes of the <i>Caenorhabditis elegans</i> nervous system for the presence of DNA binding motifs of 136 neuronally expressed <i>C. elegans</i> transcription factors. Using a phylogenetic footprinting pipeline, we identify <i>cis-</i>regulatory motif enrichments among neuron class-specific gene batteries and we identify cognate transcription factors for 117 of the 118 neuron classes. In addition to predicting novel regulators of neuronal identities, our nervous system-wide analysis at single cell resolution supports the hypothesis that many transcription factors directly co-regulate the cohort of effector genes that define a neuron type, thereby corroborating the concept of so-called terminal selectors of neuronal identity. Our analysis provides a blueprint for how individual components of an entire nervous system are genetically specified.