Members of the Lundquist lab study the molecular mechanisms of nervous system development using the nematode C. elegans as a model. In particular, researchers in the lab study how the Rac GTPases regulate the actin cytoskeleton during axon outgrowth and in growth cone morphology (in the formation of growth cone lamellipodia and filopodia). Furthermore, lab members are interested in the molecular mechanisms of neuroblast polarization and migration and the roles of receptors and ligands in the control of direction of polarization and migration as well as the role of cytoplasmic signaling molecules (e.g. GTPases, kinases) in this process. The processes of neuronal polarization and migration and axon pathfinding sculpt the structure of the mammalian central nervous system, including the human brain, so understanding conserved mechanisms of morphogenesis will be important to understanding the basis of human developmental disorders and might elucidate mechanisms of central nervous system recovery after trauma such as spinal cord injury or stroke.
Recent work has focused on the role of the Rho GTPases in neuronal development. Rho GTPases are members of signaling pathways that link guidance receptors to the cytoskeleton. the lab has identified the UNC-115 protein (called abLIM in humans), which is actin-binding protein that acts with Rho GTPases and might modulate the actin cytoskeleton directly in response to guidance signals. Other studies in the lab have identified new and previously-identified proteins that control growth cone outgrowth during development of the nervous system.
- Demarco, R.S., Struckhoff, E.C., and Lundquist, E.A. The Rac GTP exchange factor TIAM-1 acts with CDC-42 and the guidance receptor UNC-40/DCC in neuronal protrusion and axon guidance. 2012, 8:4, e1002665.
- Huarcaya Najarro, E., Wong, L., Zhen, M., Pinedo Carpio, E., Goncharov, A., Garriga, G., Lundquist, E.A., Jin, Y., and Ackley, B.D. Caenorhabditis elegans Flamingo cadherin fmi-1 regulates GABAergic neuronal development. 2012 Mar 21;32(12):4196-211.
- Alan, J.K., and Lundquist ,E.A. Analysis of Rho GTPase Function in Axon Pathfinding Using Caenorhabditis elegans. Methods Mol Bio 2012; 827:339-58.
- Norris, A.D., and Lundquist, E.A. UNC-6/Netrin and its receptors UNC-5 and UNC-40/DCC modulate growth cone protrusion in vivo in C. elegans. Development 2011, 138:4433-4442.
- Demarco, R.S. and Lundquist, E.A. Extra Views: “RACK”-ing up the effectors: receptor for activated C kinase acts downstream of Rac GTPase signaling in growth cone outgrowth. Small GTPases 2011, 2:1, 1-4.
- Demarco, R.S. and Lundquist, E.A. RACK-1 acts cell autonomously with Rac GTPase signaling and UNC-115/abLIM in C. elegans axon pathfinding and cell migration. PLOS Genetics 2010, 6:11 e1001215.
- Dyer (Chapman), J.O., Demarco, R.S., Lundquist, E.A. Distinct roles of Rac GTPases and the UNC-73/Trio and PIX-1 Rac GTP exchange factors in neuroblast protrusion and migration in C. elegans. Small GTPases 2010 1:1, pp. 44-61.
- Norris, A.D., Dyer (Chapman), J.O., and Lundquist, E.A. The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in C. elegans. Neural Development 2009, 2;4:38.
- Lundquist EA. Primer: The Finer Points of Filopodia. PLoS Biol. 2009 Jun 30;7(6):e1000142. Epub 2009 Jun 30.
- Hueston JL, Purinton Herren G, Cueva JG, Buechner M, Lundquist EA, Goodman MB, Suprenant KA. The C. elegans EMAP-like protein, ELP-1 is required for normal touch sensation and associates with microtubules and adhesion complexes. BMC Dev Biol. Nov 17;8(1):110, 2008.
- J.O. Chapman, H. Li, and E.A. Lundquist. “The MIG-15 NIK kinase acts cell-autonomously in neuroblast polarization and migration in C. elegans.” Developmental Biology, Dec 15;324(2):245-57, 2008.
- M.A. Shakir, K. Jiang, E.C. Struckhoff, R.S. Demarco, F.B. Patel, M.C. Soto, and E.A. Lundquist. “The Arp2/3 activators WAVE and WASP have distinct genetic interactions with Rac GTPases in C. elegans axon guidance.” Genetics 179(4):1957-1971, 2008. PMCID: PMC2516072.
- J. Lu, W.L. Dentler, and E.A. Lundquist. “FLI-1 Flightless-1 acts with LET-60 Ras to control germ line morphogenesis in C. elegans.” BMC Dev Biol. May 16;8:54, 2008.
- Y. Yang, J. Lu, S. Quackenbush, J. Rovnak, and E.A. Lundquist. “SWAN-1, a C. elegans WD repeat protein of the AN11 family, is a negative regulator of Rac GTPase function.” Genetics 174(4):1917-32, 2006.
- M.A. Shakir, J. Gill, and E.A. Lundquist. “Interactions of UNC-34 Enabled with Rac GTPases and the NIK kinase MIG-15 in Axon Pathfinding and Neuronal Migration in C. elegans.” Genetics 172(2); 893-913, 2006.
- Y. Yang and E.A. Lundquist. “The actin-binding protein UNC-115/abLIM controls lamellipodia and filopodia formation and neuronal morphogenesis in C. elegans.” Mol Cell Biol 25, 5158-5170, 2005.
- E.A. Lundquist. “Signal transduction: Small GTPases.” Wormbook, Jan 17: 1-18, 2006.
- M.A. Shakir and E.A. Lundquist. “Analysis of Cell Migration in Caenorhabditis elegans.” Methods Mol Biol. 294: 159-74, 2004.
- J.L. Yanowitz, M.A. Shakir, E. Hedgecock, H. Hutter, A.Z. Fire, and E.A. Lundquist. “UNC-39, the C. elegans homolog of the human myotonic dystrophy-associated homeodomain protein Six5, regulates cell motility and differentiation.” Developmental Biology 272: 389-402, 2004.