How do you build a complex brain?
Brain function relies on the proper wiring of neural circuits. There are a myriad of neurons (from 100,000 in fruit flies to 100 billion in humans) that can recognize and form connections with specific partners in the immensely crowded environment of developing brains. The precise wiring diagrams of neural circuits are thought to be directly encoded by genetic programs of brain development. Errors in these programs can result in miswired circuits leading to brain disorders.
How are complex circuits assembled during development? The developmental and evolutionary origin of brain complexity remains one of the great mysteries in biology. We aim to address these questions from a genomic perspective. We are interested in understanding how genes and genomes encode the architecture of neural circuits. Our lab combines the power of genomic technologies with the rich genetic toolbox of fruit flies to study molecular mechanisms underlying brain development. Today advances in single-cell genomics and brain connectomics allow the generation of coupled transcriptome-connectome maps of the developing circuits. They provide a nearly complete description of transcriptomes for both sides of every synaptic connection. We build and use these maps to study how neural circuits emerge during brain development and evolution. Our approaches include both genome-wide computational studies and hypothesis-driven in vivo studies. Ultimately, cracking the molecular code and logic of brain wiring could enable us to rewire neural circuits and behaviors in a controllable way.
