Our research focuses on understanding the molecular mechanisms underlying neural circuit formation during development and degeneration in aging. We use a free-living tiny roundworm, called Caenorhabditis elegans, as a model. The defined cell lineage, completely mapped connectome and rapid life cycle of this organism greatly facilitate investigating nervous system at the subcellular resolution. Combining classic genetic analysis with in vivo live imaging technique and molecular and cellular manipulations, we are discovering conserved mechanisms playing key roles in neural circuit formation, gap junction regulations and neurodegeneration.
Neural circuit formation:
The development of C. elegans nervous system resembles some critical steps of mammalian CNS development. We use a simple motor neural circuit, RME circuit, as a model to investigate the conserved mechanisms of neural circuit formation. The RME circuit controls head movement and contains four GABAergic motor neurons: RME dorsal (D), RME left (L), RME right (R), and RME ventral (V), and the development of RME circuit involves neuron-neuron, neuron-glia, and neuron-muscle interactions. Through studying the RME circuit, we are uncovering novel mechanisms regulating neuronal migration, axon/dendrite differentiation and synapse elimination.
Aging-related neurodegenerative diseases have become the hottest topics in the medical field. However, 99.6% of the drug development clinical trials for those diseases during the past decade have ended in failure. It seems that we need to rethink about the influential factors affecting the onset of these diseases. Aging, which is natural to all of us, is the most obvious one of them. However, it remains unclear what causes neurodegeneration during aging. We are using a sensitized genetic background to uncover negative and positive regulators of neurodegeneration.
Gap junction regulation:
The nervous system is made up by individual neurons connected through junction structures called synapses. There are two fundamentally different types of synapses: chemical synapses and electrical synapses (also called gap junctions). Through studies in different model organisms, we have gained rich knowledge of the development and regulation of chemical synapses. However, we still know little about how gap junctions are built during development, and what regulates the dynamics of gap junctions in functional circuits. We are investigating the molecular mechanism underlying gap junction formation and regulation in C. elegans.