Transcriptional programs of circuit assembly in the Drosophila visual system

Precise patterns of synaptic connections between neurons are encoded in their genetic programs. Here we used single-cell RNA sequencing to profile neuronal transcriptomes at multiple stages in the developing Drosophila visual system. We devised an efficient strategy for profiling neurons at multiple time points in a single pool, thereby minimizing batch effects and maximizing the reliability of time-course data. A transcriptional atlas spanning multiple stages was generated including more than 150 distinct neuronal populations; of these 88 were followed through synaptogenesis. This analysis revealed a common (pan-neuronal) program unfolding in highly coordinated fashion in all neurons, including genes encoding proteins comprising the core synaptic machinery and membrane excitability. This program is overlaid by cell type-specific programs with diverse cell recognition molecules expressed in different combinations and at different times. We propose that a pan-neuronal program endows neurons with the competence to form synapses and cell type-specific programs control synaptic specificity. Overall design: Single-cell transcriptional atlas of the developing Drosophila visual system. A transcriptional atlas covers 9 stages of pupal development (every 12 hours).