Systematic identification of wiring specificity molecules in Drosophila olfactory circuit using single cell RNA-seq

Precise neural circuit assembly is critical for appropriate function of the nervous system. A functional circuit requires proper targeting and matching of axons and dendrites of pre- and post-synaptic neurons. However, our understanding of the mechanisms that establish wiring specificity of complex neural circuit is far from complete. Drosophila olfactory system consists of ~50 classes of olfactory receptor neurons and ~50 classes of projection neurons, which form one-to-one connections in the antennal lobe, providing a powerful model to study mechanisms for wiring specificity.

Here I propose to systematically identify wiring specificity molecules in Drosophila olfactory circuit using single cell RNA-seq. I aim to establish a robust technique for single cell RNA-seq data collection from specific Drosophila neurons and create a platform for data analysis. And based on this, I plan to study how lineage-specific transcription factors regulate wiring specificity and how olfactory neuron identity is determined at the molecular level.

My proposed study has broad significance beyond olfactory circuit wiring. The wiring principles we learn from flies are likely generalizable to more complex circuits in the mammalian brain. Understanding the basic mechanisms of wiring specificity is a prerequisite to understanding how mis-wiring may contribute to neurological and psychiatric disease.