Dr. Scott Clark
Associate Professor

Genetics of axon guidance and neuronal polarity; regulation of Wnt signaling

University of Nevada
Biology Department m/s 314
Reno NV 89557

email Dr. Scott Clark

Office phone: 775-784-4483
Laboratory phone: 775-784-8021
FAX number: 775-784-1302

University of California, Berkeley
1984, A.B.

Massachusetts Institute of Technology
1992, Ph.D.

University of California, San Francisco
1993-1997, Postdoctoral Fellow

Research Interests:
Neurons are polarized cells possessing axonal and dendritic processes with distinct morphologies, cytoskeletal architectures and signaling properties. Polarity is established during neuronal differentiation and is essential for the assembly and function of the nervous system. The trajectories of axons and dendrites are shaped by growth cones at their tips responding to guidance cues in their environment. We are interested in understanding the cellular and molecular mechanisms that polarize neurons and pattern their axons and dendrites.

The nematode Caenorhabditis elegans has a simple, well-described nervous system that can be visualized at a single cell resolution in living animals using fluorescent protein reporters. Neurons in C. elegans extend processes with characteristic trajectories along the dorsoventral and/or anteroposterior (AP) body axis and form reproducible synaptic connections. Using genetic and molecular approaches, we identified several molecules that play key roles in controlling AP neuronal polarity. In particular, we showed that signaling by secreted Wnt proteins regulates AP neuronal polarity and discovered a conserved transmembrane protein, PLR-1, that governs the spatial and temporal response to Wnts by reducing the cell surface levels of the Wnt receptor Frizzled. Our current studies are directed at understanding how Wnt signaling controls neuronal polarity and how PLR-1 regulates Frizzled trafficking. We are also analyzing several other molecules that influence axon formation, extension and maintenance.

Selected Publications:
Clark, S. G. and Chiu, C. (2003). C. elegans ZAG-1, a Zn finger-homeodomain protein, regulates axonal development and neuronal differentiation. Development 130: 3781-3794.

Xue Y., Fares H., Grant B., Li Z., Rose A. M., Clark S. G. and Skolnik E. Y. (2003). Genetic analysis of the myotubularin family of phosphatases in Caenorhabditis elegans. J. Biol. Chem. 278: 34380-34386.

Cram E. J., Clark S. G. and Schwarzbauer J. E. (2003). Talin loss-of-function uncovers roles in cell contractility and migration in C. elegans. J Cell Sci. 116: 3871-3878.

Yoneda T., Benedetti C., Urano F., Clark S. G., Harding H.P. and Ron D. (2004). Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones. J Cell Sci. 117: 4055-4066.

Pan, C.-L., Howell, J. E., Clark, S. G., Hilliard, M., Cordes, S., Bargmann, C. I. and Garriga, G. (2006). Multiple Wnts and Frizzleds regulate anteriorly directed cell and growth cone migrations in Caenorhabditis elegans. Dev. Cell 10: 367-77.

Prasad, B. C. and Clark, S. G. (2006). Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Development 133: 1757-1766.

Chang, C., Adler, C. E., Krause, M., Clark, S. G., Gertler, F. B., Tessier-Lavigne, M. and Bargmann, C. I. (2006). MIG-10/Lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in response to Slit and Netrin. Current Biol. 16: 854-862

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