UCLA

Proper neural circuit formation is crucial for brain function and animal behavior. How neurons form connections with the right partners at the right subcellular locations is an essential question in neuroscience. Many mechanisms such as cell recognition, local signaling, and neural activity, have been shown to regulate neural circuit assembly, but the temporal regulation mechanisms of gene expression remain unclear. Recent improvement of single cell RNA-seq (scRNA-seq) method enables us to profile transcriptomes of many types of neurons at multiple developmental stages to study gene expression changes during neural development. By analyzing the transcriptomes of developing neurons in the Drosophila visual system, we identified that a cascade of transcription factors induced by steroid hormone ecdysone is expressed in a highly synchronized fashion in all neurons during circuit assembly. We demonstrated that disrupting the ecdysone signaling leads to specific wiring defects in multiple types of neurons. Using scRNA-seq, we profiled 5 types of lamina neurons with different genetic perturbations that disrupt the ecdysone pathway. The results showed that a common set of genes required for neuronal maturation and a cell-type specific set of genes enriched for recognition molecules are controlled by the ecdysone pathway. Cell-type specific recognition molecules can be co-regulated by the globally controlled ecdysone pathway and constantly expressed cell-type specific transcription factors (i.e. Erm). These data showed that neurons integrate a global temporal program with cell-type specific transcription factors to express distinct sets of cell recognition molecules at different time points to regulate neural circuit assembly. By coordinating when and which recognition molecules are expressed in different neurons, the global temporal program could generate more molecular codes for neural interactions and choreograph circuit assembly.