Abstract: Complex neural networks consist of many neurons with distinct identities. Though it is long appreciated that the enormous neural diversity arises in spatiotemporally patterned manners, the exact underlying molecular mechanisms remain unclear even in the relatively trackable Drosophila brain. We map cell lineages and then track changes in gene expressions and genome states along actual cell lineages to see how the genome encodes brain connectome.

Biosketch:
My background is rooted in both medicine and research, leading me to employ genetic model systems to understand human brain development. I aspire to reverse-engineer the brain by tracking development from neural stem cells to diverse neuron types. My lab has developed and applied sophisticated genetic mosaic tools to understand how the Drosophila melanogaster brain develops on the level of individual cells. Briefly, we have created lineage-restricted drivers by immortalizing the expression patterns of early patterning genes. These drivers enable us to map single neurons based on lineage origin and neuronal birth order. Indeed, we have successfully mapped the developmental sequence of entire neuronal lineages in the adult fly brain, providing unparalleled resolution and critical insight into how a limited number of progenitor cells can generate diverse
neurons. We have further successfully investigated the molecular mechanisms underlying this neuronal diversification and probed the developmental plasticity of these neurons in the adult brain. We have recently extended our approach from fly to vertebrates (including mouse and zebrafish). Nonetheless, critical gaps remain, even in our study of fly brain development. To completely understand how the genome encodes diverse neuron types, we need to track not just cell lineages, but also the dynamic developmental genes which confer cells with their specific fates. As part of this effort, we have built new, powerful, CRISPR-based genetic tools to simultaneously track birth order and acutely manipulate genes of interest. Our findings will be applied to ultimately tailor neural/brain development in order to treat neurological patients.