[Research Interests] [Representative Publications] [Lab Members] RESEARCH INTERESTSDevelopmental Genetics of the Nervous System of Caenorhabditis ElegansVarious cells in animals migrate after their birth to distant sites where they divide or differentiate. Germline and gonadal cells, for example, originate separately but move to a common site to form the reproductive primordia. Growth cones migrate along glial or axonal surfaces to bring remote neurons into contact for synaptic communication. We are using genetics and molecular biology to discover and analyze the spatial cues and navigational programs that guide complex migrations during development. Each cell or axon migration comprises a series of attachments and detachments of motile cells to stationary cells, or extracellular matrix, which support and guide their movements. Some migrations are simple dispersals away from an origin, but most follow elaborate, stereotyped trajectories that presumably require sequential responsiveness to different extrinsic cues (see Figure). To understand directed migration, we must identify the cues provided by substratum cells and establish their spatial distribution, identify complementary receptors on migrating cells and elucidate navigational programs that activate these receptors in proper sequence, and determine how receptor/ligand binding actually steers the leading edge of a cell or growth cone. Mutants with abnormal cell or axonal trajectories can identify genes involved in the generation or detection of guidance cues. Because of its cellular simplicity and excellent genetics, the free-living nematode C. elegans has proved useful for mutant analyses of developmental processes, including migrations, that depend on interactions between distinct cell types. Nearly 30 genes affecting cell migrations or axon outgrowth have been discovered to date. Some mig genes affect specific navigational steps while others are strikingly pleiotropic. Two such genes have been sequenced thus far; their deduced products are a basement membrane protein and a trans-membrane receptor, respectively. REPRESENTATIVE PUBLICATIONSIkeda DD, Duan Y, Matsuki M, Kunitomo H, Hutter H, Hedgecock EM, Iino Y. (2008). CASY-1, an ortholog of calsyntenins/alcadeins, is essential for learning in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 105(13):5260-5. Walston T, Guo C, Proenca R, Wu M, Herman M, Hardin J, Hedgecock E. (2006) . mig-5/Dsh controls cell fate determination and cell migration in C. elegans. Dev Biol. 298:485-97. Kao G, Huang CC, Hedgecock EM, Hall DH, Wadsworth WG. (2006). The role of the laminin beta subunit in laminin heterotrimer assembly and basement membrane function and development in C. elegans. Dev Biol. 290(1):211-9. Wacker I, Schwarz V, Hedgecock EM, Hutter H. (2003). zag-1, a Zn-finger homeodomain transcription factor controlling neuronal differentiation and axon outgrowth in C. elegans. Development. 130(16):3795-805. PMID: 12835395. Vogel BE, Hedgecock EM. (2001). Hemicentin, a conserved extracellular member of the immunoglobulin superfamily, organizes epithelial and other cell attachments into oriented line-shaped junctions. Development.128(6):883-94. Kipreos ET, Gohel SP, Hedgecock EM. (2000). The C. elegans F-box/WD-repeat protein LIN-23 functions to limit cell division during development. Development. 127(23):5071-82.
Recent TeachingSpring 2009. Biology 020.312 Introduction to the Human Brain This course will also be offered in the Spring 2010.
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