Zhuoran Li

All Publications

• Dimensionality reduction simplifies synaptic partner matching in an olfactory circuit. bioRxiv : the preprint server for biology Lyu, C., Li, Z., Xu, C., Wong, K. K., Luginbuhl, D. J., McLaughlin, C. N., Xie, Q., Li, T., Li, H., Luo, L. 2024

  Abstract

  The distribution of postsynaptic partners in three-dimensional (3D) space presents complex choices for a navigating axon. Here, we discovered a dimensionality reduction principle in establishing the 3D glomerular map in the fly antennal lobe. Olfactory receptor neuron (ORN) axons first contact partner projection neuron (PN) dendrites at the 2D spherical surface of the antennal lobe during development, regardless of whether the adult glomeruli are at the surface or interior of the antennal lobe. Along the antennal lobe surface, axons of each ORN type take a specific 1D arc-shaped trajectory that precisely intersects with their partner PN dendrites. Altering axon trajectories compromises synaptic partner matching. Thus, a 3D search problem is reduced to 1D, which simplifies synaptic partner matching and may generalize to the wiring process of more complex brains.

  View details for DOI 10.1101/2024.08.27.609939

  View details for PubMedID 39253519

  View details for PubMedCentralID PMC11383009

• Molecular mechanisms of proteoglycan-mediated semaphorin signaling in axon guidance. Proceedings of the National Academy of Sciences of the United States of America Nourisanami, F., Sobol, M., Li, Z., Horvath, M., Kowalska, K., Kumar, A., Vlasak, J., Koupilova, N., Luginbuhl, D. J., Luo, L., Rozbesky, D. 2024; 121 (31): e2402755121

  Abstract

  The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based on the degree of sulfation. Structural analysis of Sema2b unveiled multiple GAG-binding sites positioned outside canonical plexin-binding site, with the highest affinity binding site located at the C-terminal tail, characterized by a lysine-rich helical arrangement that appears to be conserved across secreted semaphorins. In vivo studies revealed a crucial role of the Sema2b C-terminal tail in specifying the trajectory of olfactory receptor neurons. We propose that secreted semaphorins tether to the cell surface through interactions with GAG chains of proteoglycans, facilitating their presentation to cognate receptors on passing axons.

  View details for DOI 10.1073/pnas.2402755121

  View details for PubMedID 39042673

• Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching. Cell Xu, C., Li, Z., Lyu, C., Hu, Y., McLaughlin, C. N., Wong, K. K., Xie, Q., Luginbuhl, D. J., Li, H., Udeshi, N. D., Svinkina, T., Mani, D. R., Han, S., Li, T., Li, Y., Guajardo, R., Ting, A. Y., Carr, S. A., Li, J., Luo, L. 2024

  Abstract

  In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.

  View details for DOI 10.1016/j.cell.2024.06.022

  View details for PubMedID 38996528

• Toward building a library of cell type-specific drivers across developmental stages. Proceedings of the National Academy of Sciences of the United States of America Lyu, C., Li, Z., Luo, L. 2023; 120 (35): e2312196120

  View details for DOI 10.1073/pnas.2312196120

  View details for PubMedID 37590431

• Temporal evolution of single-cell transcriptomes of Drosophila olfactory projection neurons. eLife Xie, Q., Brbic, M., Horns, F., Kolluru, S. S., Jones, R. C., Li, J., Reddy, A. R., Xie, A., Kohani, S., Li, Z., McLaughlin, C. N., Li, T., Xu, C., Vacek, D., Luginbuhl, D. J., Leskovec, J., Quake, S. R., Luo, L., Li, H. 2021; 10

  Abstract

  Neurons undergo substantial morphological and functional changes during development to form precise synaptic connections and acquire specific physiological properties. What are the underlying transcriptomic bases? Here, we obtained the single-cell transcriptomes of Drosophila olfactory projection neurons (PNs) at four developmental stages. We decoded the identity of 21 transcriptomic clusters corresponding to 20 PN types and developed methods to match transcriptomic clusters representing the same PN type across development. We discovered that PN transcriptomes reflect unique biological processes unfolding at each stage-neurite growth and pruning during metamorphosis at an early pupal stage; peaked transcriptomic diversity during olfactory circuit assembly at mid-pupal stages; and neuronal signaling in adults. At early developmental stages, PN types with adjacent birth order share similar transcriptomes. Together, our work reveals principles of cellular diversity during brain development and provides a resource for future studies of neural development in PNs and other neuronal types.

  View details for DOI 10.7554/eLife.63450

  View details for PubMedID 33427646

• Live cell fluorescence imaging reveals dynamic production and loss of bacterial flagella. Molecular microbiology Zhuang, X. Y., Guo, S., Li, Z., Zhao, Z., Kojima, S., Homma, M., Wang, P., Lo, C. J., Bai, F. 2020

  Abstract

  Bacterial flagella are nanomachines that drive bacteria motility and taxis in response to environmental changes. Whether flagella are permanent cell structures and, if not, the circumstances and timing of their production and loss during the bacterial life cycle remain poorly understood. Here we used the single polar flagellum of Vibrio alginolyticus as our model and, implementing in vivo fluorescence imaging, revealed that the percentage of flagellated bacteria (PFB) in a population varies substantially across different growth phases. In the early-exponential phase, the PFB increases rapidly through widespread production of flagella. In the mid-exponential phase, the PFB peaks at around 76% and the partitioning of flagella between the daughter cells is 1:1 and strictly at the old poles. After entering the stationary phase, the PFB starts to decline, mainly because daughter cells stop making new flagella after cell division. Interestingly, we observed that bacteria can actively abandon flagella after prolonged stationary culturing, though cell division has long been suspended. Further experimental investigations confirmed that flagella were ejected in V. alginolyticus, starting from breakage in the rod. Our results highlight the dynamic production and loss of flagella during the bacterial life cycle.

  View details for DOI 10.1111/mmi.14511

  View details for PubMedID 32259388

• Transgenic Eimeria mitis expressing chicken interleukin 2 stimulated higher cellular immune response in chickens compared with the wild-type parasites FRONTIERS IN MICROBIOLOGY Li, Z., Tang, X., Suo, J., Qin, M., Yin, G., Liu, X., Suo, X. 2015; 6: 533

  Abstract

  Chicken coccidiosis, caused by Eimeria sp., occurs in almost all poultry farms and causes huge economic losses in the poultry industry. Although this disease could be controlled by vaccination, the reduced feed conservation ratio limits the widespread application of anticoccidial vaccines in broilers because some intermediate and/or low immunogenic Eimeria sp. only elicit partial protection. It is of importance to enhance the immunogenicity of these Eimeria sp. by adjuvants for more effective prevention of coccidiosis. Cytokines have remarkable effects on the immunogenicity of antigens. Interleukin 2 (IL-2), for example, significantly stimulates the activation of CD8+ T cells and other immune cells. In this study, we constructed a transgenic Eimeria mitis line (EmiChIL-2) expressing chicken IL-2 (ChIL-2) to investigate the adjuvant effect of ChIL-2 to enhance the immunogenicity of E. mitis against its infection. Stable transfected EmiChIL-2 population was obtained by pyrimethamine selection and verified by PCR, genome walking, western blotting and indirect immunofluorescence assay. Cellular immune response, E. mitis-specific IFN-γ secretion lymphocytes in the peripheral blood mononuclear cells, stimulated by EmiChIL-2 was analyzed by enzyme-linked immunospot assay (ELISPOT). The results showed that EmiChIL-2 stimulated a higher cellular immune response compared with that of the wild-type parasite infection in chickens. Moreover, after the immunization with EmiChIL-2, elevated cellular immune response as well as reduced oocyst output were observed These results indicated that ChIL-2 expressed by Eimeria sp. functions as adjuvant and IL-2 expressing Eimeria parasites are valuable vaccine strains against coccidiosis.

  View details for DOI 10.3389/fmicb.2015.00533

  View details for Web of Science ID 000356312600001

  View details for PubMedID 26082759

  View details for PubMedCentralID PMC4451583