Scott Clark, Ph.D.
- University of California, Berkeley 1984, A.B.
- Massachusetts Institute of Technology 1992, Ph.D.
- University of California, San Francisco 1993-1997, Postdoctoral Fellow
Neurons are polarized cells possessing axonal and dendritic processes with distinct morphologies, cytoskeletal architectures and signaling properties. 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 molecular mechanisms that polarize neurons and pattern their axons and dendrites.
The nematode Caenorhabditis elegans has a simple nervous system that can be visualized at a single cell resolution in living animals using fluorescent protein reporters. Using genetic and molecular approaches, we identified several proteins that play key roles in regulating the polarity of neurons along the anteroposterior body axis. In particular, we found that Wnt signaling controls anteroposterior neuronal polarity and discovered a conserved transmembrane protein that reduces Wnt signaling by affecting the trafficking of Wnt receptors. We are also analyzing several other proteins that influence axon growth or neuronal gene expression.
- Moffat L. L., Robinson R. E., Bakoulis A. and Clark S. G. (2014). The conserved transmembrane RING finger protein PLR-1 downregulates Wnt signaling by reducing Frizzled, Ror and Ryk cell-surface levels in C. elegans. Development 141:617-628.
- Singhvi, A., Teuliere, J., Talavera, K., Cordes, S., Ou, G., Vale, R. D., Prasad, B. C., Clark, S. G. and Garriga, G. (2011). The Arf GAP CNT-2 regulates the apoptotic fate in C. elegans asymmetric neuroblast divisions. Current Biol. 21:948-954.
- Pan, C.-L., Baum, P.D., Gu, M., Jorgensen, E. M., Clark, S. G. and Garriga, G. (2008). C. elegans AP-2 and retromer control Wnt signaling by regulating MIG-14/Wntless. Dev Cell 14:132-139.
- 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.
- Prasad, B. C. and Clark, S. G. (2006). Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans. Development 133: 1757-1766.
- 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: 367-377.
- 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.