Neuronal subtype specification is regulated by the coordinated action of transcription factors. Any one factor may be expressed in multiple subtypes, but specification is achieved based on the precise combination of factors and is therefore context dependent. In this issue (), Oliver Hobert and colleagues explore neuronal differentiation in C. elegans and focus on the role of the TTX-3 LIM homeodomain transcription factor in regulating neural subtype specification. The authors find that TTX-3 is broadly required in multiple neuron classes of relatively unrelated identity, but that the interacting partners and downstream targets of TTX-3 are subtype specific. TTX-3 is required for cholinergic AIY interneuron specification, while an interaction with the POU domain protein UNC-86 leads to the specification of serotinergic NSM neurons. Furthermore, UNC-86 itself can specify cholinergic IL2 sensory and URA motoneurons via cooperation with the ARID-type transcription factor CFI-1. This detailed analysis of transcriptional cascades reveals a programming roadmap for neuronal subtype specification.
