Identify molecular pathways involved in branching
Using mammalian neuronal cell models, we investigate known factors in controlling stereotypic branched patterns and search new genes that are critical to regulating different aspects of branching. A variety of modern molecular techniques are combined with primary cell culture and in vivo analysis in these studies. For examples, a) following sensory neurons in the dorsal root ganglion (DRG) during early development, we have identified two signaling mechanisms that are required for proper bifurcation; and b) using a viral delivery technique to inactivate gene function while simultaneously visualizing single cell morphology, we have identified a cell surface signaling system required for cerebellar Purkinje cell dendrite self-avoidance, a patterning mechanism generating elaborated branches that rarely overlap.
Explore cell biological regulation of branching
Although branched morphologies come in different shape and size, only a limited number of factors are encoded by the genome. To understand how different branching patterns are generated by a combination of environmental cues and genetic programs, we investigate the cooperation of molecules that regulates different steps of branching, including initiation, growth, guidance, stabilization, and patterning. Cutting-edge cell biological tools including live cell imaging are employed for these studies. Recently, we developed a novel computer vision method that allows us to rapidly analyze microtubule assembly and regulation in neurons.
Define the contribution of branching to circuit function and repair
Branching morphogenesis is critical to generating complex neural networks, but what is the physiological consequence when branching regulation is perturbed? How are they affected in neurological and psychiatric diseases? Knowledge of molecular pathways coupled to the structurally robust phenotypes offers us a unique opportunity to investigate the contribution of nerve branching to normal circuit functions. In addition, we are interested in the response of nerve branches to degeneration and their regenerative potentials after injury.