All Publications

  • A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans ELIFE Zou, W., Shen, A., Dong, X., Tugizova, M., Xiang, Y. K., Shen, K. 2016; 5


    Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a multi-protein receptor-ligand complex that also contains two transmembrane ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA-1. The activation of DMA-1 strictly requires all three ligands, which establishes a combinatorial code to precisely target and pattern dendritic arbors.

    View details for DOI 10.7554/eLife.18345

    View details for Web of Science ID 000387035300001

    View details for PubMedCentralID PMC5079751

  • MTM-6, a Phosphoinositide Phosphatase, is Required to Promote Synapse Formation in Caenorhabditis elegans PLOS ONE Ericson, V. R., Spilker, K. A., Tugizova, M. S., Shen, K. 2014; 9 (12)


    Forming the proper number of synapses is crucial for normal neuronal development. We found that loss of function of the phosphoinositide phosphatase mtm-6 results in a reduction in the number of synaptic puncta. The reduction in synapses is partially the result of MTM-6 regulation of the secretion of the Wnt ligand EGL-20 from cells in the tail and partially the result of neuronal action. MTM-6 shows relative specificity for EGL-20 over the other Wnt ligands. We suggest that the ability of MTM-6 to regulate EGL-20 secretion is a function of its expression pattern. We conclude that regulation of secretion of different Wnt ligands can use different components. Additionally, we present a novel neuronal function for MTM-6.

    View details for DOI 10.1371/journal.pone.0114501

    View details for Web of Science ID 000346907200096

    View details for PubMedID 25479419

    View details for PubMedCentralID PMC4257696

  • Caenorhabditis elegans Muscleblind homolog mbl-1 functions in neurons to regulate synapse formation NEURAL DEVELOPMENT Spilker, K. A., Wang, G. J., Tugizova, M. S., Shen, K. 2012; 7


    The sequestration of Muscleblind splicing regulators results in myotonic dystrophy. Previous work on Muscleblind has largely focused on its roles in muscle development and maintenance due to the skeletal and cardiac muscle degeneration phenotype observed in individuals with the disorder. However, a number of reported nervous system defects suggest that Muscleblind proteins function in other tissues as well.We have identified a mutation in the Caenorhabditis elegans homolog of Muscleblind, mbl-1, that is required for proper formation of neuromuscular junction (NMJ) synapses. mbl-1 mutants exhibit selective loss of the most distal NMJ synapses in a C. elegans motorneuron, DA9, visualized using the vesicle-associated protein RAB-3, as well as the active zone proteins SYD-2/liprin-? and UNC-10/Rim. The proximal NMJs appear to have normal pre- and postsynaptic specializations. Surprisingly, expressing a mbl-1 transgene in the presynaptic neuron is sufficient to rescue the synaptic defect, while muscle expression has no effect. Consistent with this result, mbl-1 is also expressed in neurons.Based on these results, we conclude that in addition to its functions in muscle, the Muscleblind splice regulators also function in neurons to regulate synapse formation.

    View details for DOI 10.1186/1749-8104-7-7

    View details for Web of Science ID 000304541600001

    View details for PubMedID 22314215

    View details for PubMedCentralID PMC3353867

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