Elke Stein

Assistant Professor, Molecular, Cellular & Developmental Biology, and Cell Biology
Stein lab website Phone: (203) 432-8402 (KBT-232) Lab: (203) 432-7651 (KBT-244) Fax: (203) 432-6161 e-mail: elke.stein@yale.edu		Department of Molecular Cellular and Developmental Biology 219 Prospect Street PO Box 208103 New Haven, CT 06520-8103 <Courier Address> 219 Prospect Street, KBT-232 New Haven, CT 06511-2106

One of the earliest steps in neuronal development is the growth of axons from their cell bodies of origin to their appropriate targets, to form a precise pattern of neuronal connections. The growth of axons is highly directed, as axons are guided to their targets by specific guidance cues displayed in the extracellular environment. These cues can be attractive, steering axons towards particular sources of the cues, or repulsive, steering axons away from inappropriate regions. We are interested in identifying attractive and repulsive guidance cues for developing axons, elucidating their precise functions in guiding axons in vivo, and determining how axons respond to these cues with directed growth. Recent progress in the field lead to the identification of several families of attractants and repellents, including the netrin, semaphorin and slit protein families, as well as receptors involved in mediating the responses of these factors, however only little is known how these guidance cues function in vivo.

We are currently focusing on several guidance systems, including the netrin receptors DCC and UNC-5 and the DSCAM (Down syndrome cell adhesion molecule) family of orphan receptors. Our current efforts are aimed at 1) elucidating their functions in vivo using gene targeting and transgenic approaches, and 2) in identifying the signal transduction mechanisms through which these receptors trigger axonal steering, branching of axons and dendrites and exploring their role in synaptogenesis. To address this we are using a series of biochemical, cell biological and molecular techniques, in combination with functional approaches, including an axon turning assays utilizing Xenopus spinal and neuronal rodent cultures, in vitro explant and slice cultures, and in vivo assays using the developing chicken as a model.

Selected Publications
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Stein E., Lane A .A., Cerretti D.P., Schoecklmann H.O., Schroff A.D., VanEtten R.L. and Daniel T.O. (1998) Eph receptors discriminate specific ligand oligomers to determine alternative signaling complexes, attachment, and assembly responses. Genes & Development 12: 667-678.  

Hong K., Hinck L. Nishiyama M., Poo M-M., Tessier-Lavigne M. and Stein E. (1999) A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion. Cell 97: 927-941  

Stein E. and Tesier-Lavigne M. (2001) Hierarchical organization of guidance receptors: Silencing of netrin attraction by slit through a Robo/DCC receptor complex. Science 291: 1928-1938  

Stein E., Zou Y., Poo .M-M. and Tessier-Lavigne M. (2001) Binding of DCC by netrin-1 to mediate axon guidance independent of Adenosine A2B receptor activation. Science 291: 1976-1982  

Cheng H-J., Bagri A., Yaron A, Stein E., Pleasure S.J. and Tessier-Lavigne. (2001) Plexin-A3 Mediates Semaphorin Signaling and Regulates the Development of Hippocampal Axonal Projections. Neuron 32: 249-263.  

Whitford K.L., Marillat V., Stein E., Goodman C.S., Tessier-Lavigne M., Chedotal A. and Ghosh A. (2002) Regulation of cortical dendrite development by Slit-Robo interactions. Neuron 33: 47-61.  

Forcet C., Stein E., Pays L., Llambi F., Corset V., Tessier-Lavigne M. and Mehlen P. (2002) DCC-dependent MAPK activation is required for netrin-1 mediated axon outgrowth. Nature 417: 443-447.  

Charron F., Stein E., Jeong J., McMahon A.P. and Tessier-Lavigne M. (2003) The morphogen Sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113: 11-23.  

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