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The L1CAM family of cell adhesion molecules is important for nervous system development and function. Mutations in L1CAM are linked to the L1 neurological disorder, autism, and neuropsychiatric disorders, including schizophrenia and addiction. To better understand how impaired L1CAM functions result in nervous system dysfunction, the Chen lab uses C. elegans as a genetic model organism to dissect L1CAM roles and mechanisms of action. Current projects are focused on the two C. elegans L1CAM genes, lad-1/sax-7 and lad-2, which have non-overlapping functions in maintaining neural organization and axon guidance, respectively.
In dissecting how SAX-7 maintains neural architecture throughout the life of an animal, we determined anchorage of SAX-7 to the dystrophin- and spectrin-actin cytoskeletons is important. This finding may provide insight into why a large percentage of Duchenne Muscular Dystrophy patients with impaired dystrophin function also suffer from cognitive deficits and neuropsychiatric disorders besides muscle dystrophy. In addition to neural organization maintenance, we recently identified a novel role for sax-7 that impinges on synaptic function. We are currently using molecular genetic approaches to identify this novel sax-7 function.
Having identified LAD-2 as a receptor that mediates targeted axon migration, we are focusing on 1) identifying guidance cues to which LAD-2 responds and 2) determining how LAD-2 integrates and translates these extracellular guidance signals intracellularly.
Dong, B., Moseley-Alldredge, M., Schwieterman, A.A., Donelson, C.J., McMurry, J.L., Hudson, M.L., and Chen, L. EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans. Development 143: 1182-91. PMCID: PMC4852490
Opperman, K., Moseley-Alldredge, M., Yochem, J., Bell, L., Kanayinkal, T., and L. Chen. 2015. A novel nondevelopmental role of the SAX-7/L1CAM cell adhesion molecule in synaptic regulation in C. elegans. Genetics 199:497
Zhou, S., and Chen, L. 2011. Neural integrity is maintained by dystrophin in C. elegans. J. Cell Bio. 192: 349-63.
Zhou, S. and Chen, L. 2010. “CRASH’ing with the worm—insights into L1CAM functions and mechanisms” invited review for Developmental Dynamics 239: 1490-501.
Zhou, S., Opperman, K., Wang, X., and Chen, L. (2008). unc-44 ankyrin and stn-2 γ-syntrophin regulate sax-7 L1CAM function in maintaining neuronal positioning in Caenorhabditis elegans. Genetics 180: 1429-1443.
Wang, X., Zhang, W., Cheever, T., Opperman, K., Schwarz, J. Hutter, H. Koepp D., and Chen, L. (2008). The C. elegans L1CAM homologue, LAD-2, functions as a co-receptor in MAB-20/Sema2-mediated axon guidance.” Journal of Cell Biology 180: 233-46.
Wang, X, Kweon, J, Larson, S and Chen, L. (2005) A role for the C. elegans L1CAM homologue lad-1/sax-7 in maintaining tissue attachment. Developmental Biology 284: 273-291.
Chen, L., Ong, B. and Bennett, V. (2001) LAD-1, the C. elegans L1CAM family homologue, has essential cell adhesion roles in the early embryo, participates in cell migration, and is a substrate for phosphotyrosine-based signaling. Journal of Cell Biology 154: 841-855.