Our central focus is understanding the mechanisms that underlie neuronal growth cone guidance. Repulsive guidance events play an important role in directing axons to their targets but are not well understood. We have devoted most of our efforts towards cellular and molecular analyses of proteins belonging to the semaphorin gene family, several members of which function as potent repulsive cues during neural development. Many proteins which influence axon guidance decisions, including certain semaphorins, are expressed in the adult nervous system. Since repulsive or inhibitory cues can prevent robust axonal regeneration, this work will contribute towards therapeutic strategies designed to promote axonal regeneration following neuronal injury or degeneration. As part of our exploration of semaphorin-mediated neuronal guidance events in both Drosophila and rodents, we have discovered novel semaphorin receptors and defined the cellular contexts in which both short- and long-range guidance events orchestrate the establishment of neuronal connectivity. We have also defined phylogenetically conserved intrinsic and extrinsic factors which serve to determine whether semaphorin guidance cues will function as repellents or attractants. In addition, we have addressed how these conserved signaling cascades function in vascular development. It is our goal to determine how repulsive and attractive guidance cues transmit their guidance information to the growth cone cytoskeleton and thereby guide neuronal and non-neuronal cells to their appropriate targets.

Publications:

Ayoob, J.C., Terman, J.R., and Kolodkin, A.L. (2006). Drosophila Plexin B is a Sema-2a receptor required for axon guidance. Development, 133, 2125-2135.

Huber, A.B., Kania, A., Tran, T.S., Gu, C., De Marco Garcia, N., Lieberam, I., Johnson, D., Jessell, T.M. Ginty, D.D., and Kolodkin, A.L. (2005). Distinct roles for secreted semaphorin signaling in spinal motor axon guidance. Neuron, 48, 949-964.

Kantor, D.B., Chivatakarn, O., Peer, K.L., Oster, S.F., Inatani, M., Hansen, M.J., Flanagan, J.G., Yamaguchi, Y., Sretavan, D.W., Giger, R.J., and Kolodkin, A.L. (2004). Semaphorin 5A is a Bifunctional Axon Guidance Cue Regulated by Heparan and Chondroitin Sulfate Proteoglycans. Neuron, 44, 961-975.

Terman, J.R., and Kolodkin, A.L. (2004). The AKAP Nervy direction couples Protein Kinase A to Plexin-mediated semaphorin repulsion. Science, 303, 1204-1207.

Pasterkamp, R.J., Peshon, J.J., Spriggs, M.K. and Kolodkin, A.L. (2003). Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature, 424, 398-405.