How different structural and functional compartments form in a cell is a fundamental problem in biomedical research. This problem is especially acute in the nervous system, where there are thousands of types of neurons that differ in morphology and function and thus in their subcellular compartmentalization. Understanding how distinct subcellular compartments of neurons are established will provide critical insights to the assembly, function, plasticity, and disorders of the nervous system.
We are interested in how dendrites and axons, two major compartments that ensure directional information flow in a neuron, develop differently, and how dendrites become further compartmentalized into distinct functional domains. To study these problems, a major system that we have been using is the Drosophila dendritic arborization neurons, which elaborate their dendritic arbors in the body wall in a near two-dimensional fashion and thus allow for high resolution imaging of intracellular events in live, intact larvae. Taking advantage of the superb Drosophila genetics, we have carried out genetic screens and various types of analyses to identify the molecular mechanisms underlying differential development of dendrites and axons. We also complement the Drosophila system with cultured hippocampal neurons from rat embryos, a well-established system for neuronal cell biology, to both extend the mechanistic studies and investigate the evolutionary conservation of such mechanisms. Using these approaches, we have studied how membrane systems, especially the secretory pathway (e.g. dendritic Golgi outposts), contribute to the differential development of dendrites and axons.
We plan to both extend the studies on membrane systems and explore new aspects of neuron compartmentalization in the context of developing, functioning, and diseased neural circuits.
