University of California, San Diego
About University of California, San Diego
Yimin Zou's lab at University of California, San Diego studies axon guidance, synapse formation, injury and repair of the central nervous system. We are interested in axon guidance cues that provide directional information and identified the Wnt family proteins as key guidance molecules along the major axes of the central nervous system for axon pathfinding and topographic mapping. We are currently studying how these guidance cues are laid out in concentration gradients and how axonal growth cones recognize and respond to these gradients. We found that the conserved apical-basal and planar cell polarity pathways mediate growth cone turning and an apical-basal polarity signaling component, aPKC, promotes the endocytosis of a Wnt/planar cell polarity component, Frizzled3. We are testing whether this is part of an amplification mechanism for asymmetric signaling to polarize growth cones. Traumatic injuries of the adult brain and the spinal cord lead to loss of many important functions. We found that the Wnt signaling pathways are reactivated after spinal cord injury. The reinduced Wnt inhibitory system limits the sprouting of corticospinal tract collateral branches and regenerative growth of sensory axons and thus inhibits functional recovery. Our recent studies showed that combining molecular manipulation to enhance axon plasticity with behaviorally-guided training lead to the maximal functional recovery. We are currently studying the network basis of neural circuit remodeling after spinal cord injury. The signaling mechanisms that assemble neuronal synapses have been elusive. Our recent finding suggests that planar cell polarity signaling components play essential roles in glutamatergic synapse formation. This opens up new opportunities to better understand synaptogenesis and plasticity, fundamental to neural circuit function and diseases. We recently received a collaborative BRAIN Initiative grant to characterize all spinal cord neurons that are connected with various structures of the brain by single cell transcriptomics, morphology, electrophysiology and connectivity. My lab has extensive experience in studying the development and function of many neuronal cell types, including cortical and hippocampal neurons, retinal ganglion cells, spinal cord commissural neurons, spinal cord motor neurons and dorsal root ganglion neurons. We perform organotypic or dissociated cultures to study molecular and cellular mechanisms using advanced imaging techniques, such as super resolution microscopy (STORM). We are experienced with knockout and transgenic approaches and are applying the CRISPR-Cas9 system in many of our studies. We incorporate proteomics and transcriptome analyses as part of our strategies. We carry out behavior studies, electrophysiology and optogenetics and recently started two-photon imaging of dendritic spines and calcium imaging of awake behaving animals with both two-photon microscope and miniature microscope.