How different structural and functional compartments are formed in a cell is a fundamental problem in biomedical research. This problem is especially acute in the nervous system, where there are thousands of neuron types 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.
The dendrite-axon difference: The dendrites and axons of Drosophila neurons are distinct in morphology, function, and intracellular composition. Shown here is a neuron in the peripheral nervous system of Drosophila larva. A dendrite-specific protein (Nod-β-galactosidase) was introduced into this neuron together with the diffusible green fluorescent protein. Nod-β-galactosidase is restricted in the somato-dendritic region and excluded from the axon.
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, we use Drosophila dendritic arborization neurons, which elaborate their dendrites 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 also identified a novel transcription factor (termed Dar1) dedicated for dendrite, but not axon, development, which suggests that dendrite and axon development are separated at the transcriptional level.
Genetic programs that differentiate dendrite development from axon development: From a genetic screen, we isolated many Drosophila mutants that displayed defects in either dendrites or axons. Shown here is one mutant with its dendritic arbor preferentially reduced (dar mutant) and one mutant that exhibits axon-specific defects. (CLICK ON IMAGE TO ENLARGE)
We are currently investigating: 1) the transcriptional programs and signaling pathways that separate dendrite and axon development; 2) functions and regulations of membrane trafficking through dendritic Golg outposts; and 3) circuit development of somatosensory system.