Regulatory logic of neuronal diversity: Terminal selector genes and selector motifs

Individual neuronal cell types are defined by the expression of unique batteries of terminal differentiation genes. The elucidation of the cis-regulatory architecture of several distinct, single neuron type-specific gene batteries in Caenorhabditis elegans has revealed a strikingly simple cis-regulatory logic, in which small cis-regulatory motifs are activated in postmitotic neurons by autoregulating transcription factors (TFs). Loss of the TFs results in the loss of the identity of the individual neuron type. I propose to term these TFs "terminal selector genes" and their cognate cis-regulatory target sites "terminal selector motifs." Terminal selector genes assign individual neuronal identities by directly controlling the expression of downstream, terminal differentiation genes and act in specific regulatory network configurations. The simplicity of the cis-regulatory logic on which the terminal selector gene concept is based may contribute to the evolvability of neuronal diversity.