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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.
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Zheng Y, Wildonger J, Ye B, Zhang Y, Kita A, Younger S, Zimmerman S, Jan LY, and Jan YN (2008) Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. Nature Cell Biology, Accepted for publication.
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Ye B*, Zhang Y*, Song W, Younger S, Jan LY, Jan YN (2007) Growing dendrites and axons differ in their reliance on the secretory pathway. Cell 130:717–729 (*equal contributors).
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Grueber W, Ye B, Yang C-H, Younger S, Borden K, Jan L, Jan YN (2007) Projections of Drosophila multidendritic neurons in the central nervous system: Links with peripheral dendrite morphology. Development 134:55–64.
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Ye B*, Zhang Y*, Jan LY, Jan YN (2006) The secretory pathway and neuron polarization. Journal of Neuroscience 26:10631–10632 (*equal contributors). (Review)
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Ye B, Jan YN (2006) Visualizing the breaking of symmetry. Developmental Cell 10:411–412. (Review)
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Grueber WB, Yang CH, Ye B, Jan YN (2005) The development of neuronal morphology in insects. Current Biology 15:R730–R738. (Review)
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Ye B, Jan YN (2005) Cadherins and stabilization of dendrites. Trends in Cell Biology 15:64–67. (Review)
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Ye B, Petritsch C, Clark IE, Gavis ER, Jan LY, Jan YN (2004) Nanos and pumilio are essential for dendrite morphogenesis in Drosophila peripheral neurons. Current Biology 14:314–321.
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Grueber WB*, Ye B*, Moore AW, Jan LY, Jan YN (2003) Dendrites of distinct classes of Drosophila sensory neurons show different capacities for homotypic repulsion. Current Biology 13:618–626 (*equal contributors).
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