The large diversity of cell types in nervous systems presents a challenge in identifying the genetic mechanisms that encode it. Here, we report that nearly 200 distinct neurons in the Drosophila visual system can each be defined by unique combinations of on average 10 continuously expressed transcription factors. We show that targeted modifications of this terminal selector code induce predictable conversions of neuronal fates that appear morphologically and transcriptionally complete. Cis-regulatory analysis of open chromatin links one of these genes to an upstream patterning factor that specifies neuronal fates in stem cells. Experimentally validated network models describe the synergistic regulation of downstream effectors by terminal selectors and ecdysone signaling during brain wiring. Our results provide a generalizable framework of how specific fates are implemented in postmitotic neurons.
Drosophila Proteins , Drosophila melanogaster , Neural Stem Cells , Neurogenesis , Neurons , Optic Lobe, Nonmammalian , Transcription Factors , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Gene Expression Regulation, Developmental , Neurons/physiology , Transcription Factors/genetics , Transcription Factors/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Optic Lobe, Nonmammalian/cytology , Optic Lobe, Nonmammalian/growth & development , Optic Lobe, Nonmammalian/metabolism
