A Global Temporal Genetic Program for Neural Circuit Formation

Wiring a complex brain relies on cell-type and temporal specific expression of genes encoding cell recognition molecules regulating circuit formation1−3. Though genetic programs driving cell type specificity have been described4−6, how precise temporal control is achieved remains unknown. Here, we describe a global program for the temporal regulation of cell type specific wiring genes in the Drosophila visual system. We show that the Ecdysone Receptor induces a synchronous cascade of transcription factors in neurons throughout the visual system in a highly stereotyped fashion. Single cell RNA seq analysis of neurons lacking transcription factors in the cascade revealed that targets are cell type dependent and these are enriched for wiring genes. Knock down of different transcription factors in this cascade led to defects in sequential steps in wiring. Taken together, this work identifies a synchronous, global program for temporal control of different sets of wiring genes in different neurons. We speculate that this global program coordinates development across cell types to choreograph specific steps in circuit assembly.