Rick Horwitz Faculty of Biology Phone: (434)243-6813 Fax: (434)982-3912 Office: Jordan Hall Email: horwitz@virginia.edu Homepages: http://www.people.virginia.edu/~afh2n http://www.cellmigration.org

Research Interest

Cell adhesion and migration are the foci of our research program. This
interest stems from the pivotal role that they play in a variety of
developmental phenomena. Adhesion, for example, not only holds tissues
together; but it also contributes to their formation and initiates signals
that regulate proliferation, differentiation, survival, and migration of
component cells. Migration plays a similarly critical role. During
development cells migrate from their birthplaces to distant locations where
they then differentiate. In the nervous system, directed migrations carry
neuronal growth cones to their targets where they form synaptic connections
with appropriate target cells.
Our lab is actively studying the mechanisms that underlie directed cell
migration. This includes fundamental cellular mechanisms as well as the
mechanisms that guide cells to their targets during development. Our present focus is the adhesive and migratory properties of muscle and nerve cells, since adhesive phenomena and migrations are so robust in these cells. In one initiative,
we have developed imaging techniques for visualizing, at high temporal and
spatial resolution, both the pathways that cells navigate and the
accompanying dynamics of migration-related molecules during migration in
vivo. We are doing this using three systems: a) muscle cell migration from
their embryonic origin in the somites to their targets in the limb, b)
migration from the subventricular zone in the brain to the olfactory bulb, c) tangential migration of cerebellar cells, and d) extension of axons from spinal interneurons.
Another initiative addresses the adhesive and signaling mechanisms that underlie synapse formation using hippocampal neurons. In these studies we are focusing of signaling proteins like GIT1.

Some Representative Publications:

1. Galileo, D.S., Majors, J., Horwitz, A., and Sanes, J.R. (1992) Retrovirally-introduced antisense integrin RNA inhibits radial migration of neuroblasts in vivo. Neuron 9, 1117-1131.

2. McDonald, K.M., Horwitz, A.F., and Knudsen, K.A. (1995) Adhesion molecules and skeletal myogenesis. Seminars in Developmental Biology 6, 105-116.

3. Lauffenburger, D. and Horwitz, A. (1996) Cell Migration: A physically integrated molecular process. Cell 84, 1-20.

4. Sastry, S., Lakonishok, M., and Horwitz, A.F. (1996) Integrin a subunit ratios, cytoplasmic domains, and growth factor synergy regulate muscle proliferation and differentiation: J. Cell Biol. 133, 169-184.

5. Sastry, S. and Horwitz, A. (1996) Adhesion-growth factor interactions during differentiation: An integrated biological response. Dev. Biol. 180, 455-467.

6. Horwitz, A.F. (1997) Integrins and Health. Scientific American 276, 68-75.

7. Sastry, S.K., Lakonishok, M., Wu, S., Truong, T.T., Huttenlocher, A, Turner, C.E., and Horwitz, A., (1999) Quantitative Changes in Integrin and Focal Adhesion Signaling Regulate Myoblast Cell Cycle Withdrawal. J Cell Biol. 144, 1295-1309.

8. Horwitz, A.R. and Parsons. J.T. (1999) Cell Migration: Movin' on. Science 286, 1102 -1103.

9. Knight, B, Laukaitis, C., Akhtar, N., Hotchin, N.A., Edlund, M., and Horwitz, A.F. (2000) Visualizing muscle cell migration. Current Biology, 10, 576-585, 2000.

10. Christina M. Laukaitis, Donna J. Webb, Karen Donais, and Alan F. Horwitz Differential Dynamics of 5 Integrin, Paxillin, and -Actinin during Formation and Disassembly of Adhesions in Migrating Cells J. Cell Biol. 153: 1427-1440, 2001.

11. Manabe R, Whitmore L, Weiss JM, Horwitz AR Identification of a Novel Microtubule-Associated Protein that Regulates Microtubule Organization and Cytokinesis by Using a GFP-Screening Strategy. Curr Biol. 12:1946-51, 2002.

12. Manabe Ri R, Kovalenko M, Webb DJ, Horwitz AR. GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration. J Cell Sci. 115, 1497-510, 2002.

13. Murase S, Horwitz AF. Deleted in colorectal carcinoma and differentially expressed integrins mediate the directional migration of neural precursors in the rostral migratory stream. J Neurosci. 22:3568-79 (2002).

For more information email: horwitz@virginia.edu