Assistant Professor
Ph.D., University of Wisconsin-Madison, 1993
Postdoctoral Researcher, University of California, Berkeley, 1993 - 1998

Phone: 812/856-5304
Fax: 812/855-6082
Email Wayne

Forrester Lab Website

Research Interests
Cell migration is essential for metazoan development. For example, heart, gonad and skin development all involve extensive migration of cells. Cell migration is particularly important during nervous system development. Most neurons migrate extensively from their sites of birth to the sites that they occupy in the mature animal. In a related process, neuronal growth cones migrate to their targets to generate the connectivity of the nervous system. Finally, migration of metastatic cancer cells involves many of the same proteins as other migrating cells. Our goal is to understand how migrating cells recognize and respond to the cues that direct their migrations.

Research Projects
We use a combination of genetic, molecular and genomic approaches to understand the functions of genes required for cell migration. To study cell migration, we sought genes that are required for the process using the small nematode Caenorhabditis elegans as a model system. In genetic screens, we have found 60+ mutations that are required for cell migration. Much of our effort is directed towards understanding the function of cam-1 and cfz-2, two of the gene identified in our screens. We also have initiated a functional genomic screen to identify other genes that are required for cell migration.

cam-1 appears to have at least two functions during development. First, cam-1 specifies the position of migrating cells; in cam-1 mutants cells generally migrate to positions more anterior than normal. Second, cam-1 orients the polarity of several cells. cam-1 encodes a receptor tyrosine kinase (RTK) most similar to the Drosophila and vertebrate Ror RTKs. Mutations in one of the two human Ror genes, hRor2, lead to either of two developmental syndromes – recessive Robinow syndrome or dominant brachydactyly b – that are characterized by defects in bone development. To understand Ror function in C. elegans, we are using genetic and biochemical approaches to identify other members of the cam-1 signal transduction pathway. Our ultimate aim is to understand the mechanisms by which cam-1 specifies the final position of migrating cells and how it orients the polarity of asymmetrically dividing cells.

cfz-2 encodes a C. elegans Frizzled protein that presumably functions as a receptor for Wnt signaling molecules. Wnt signaling is implicated in many developmental events, and has been implicated in the development of cancer as well. We have identified multiple Wnt molecules that may act as ligands for CFZ-2 protein to direct migrating cells to their proper positions.

Zinovyeva, A. Y., Graham, S., Cloud, V. and Forrester, W. C. 2006. The C. elegans histone deacetylase HDA-1 is required for cell migration and axon pathfinding. Dev. Biol. 289: 229-42.

Quinn, C. C., Chen, E., Stovall, E. L., Harden, M. V., Gavin, M. K., Forrester, W. C., Ryder, E. F., Soto, M. C. and Wadsworth, W. G. 2006. UNC-6/Netrin and SLT-1/Slit guidance cues orient axon outgrowth mediated by MIG-10/RIAM/Lamellipodin. Curr. Biol. 16: 845-53.

Zinovyeva, A. Y. and Forrester, W. C. 2005. The C. elegans Frizzled CFZ-2 is required for cell migration and interacts with multiple Wnt signaling pathways. Dev. Biol. 285: 447 - 61.

Forrester, W. C., Kim, C. and Garriga, G. 2004. The Caenorhabditis elegans Ror RTK CAM-1 inhibits EGL-20/Wnt signaling in cell migration. Genetics. 168: 1951-1962.

Kim, C. and Forrester, W. C. 2003. Functional analysis of the domains of the C. elegans Ror receptor tyrosine kinase CAM-1. Dev. Biol. 264: 376-390.

Forrester, W. C. 2002. The Ror receptor tyrosine kinase family. CMLS. 59: 83 - 96.

Forrester, W. C., Perens, E. and Garriga, G. 1999. cam-1, a Ror receptor tyrosine kinase required for cell migration and polarity. Nature 400: 881-885.