2003 Director's Summary Synopsis

AXON GROWTH AND GUIDANCE
Vance Lemmon, Ph.D. • John L. Bixby, Ph.D.• Ina B. Wanner, Ph.D. • Patrick M. Wood, Ph.D.

Currently, an important question in spinal cord repair is how to influence nerve fibers to regenerate across long distances and make meaningful connections. During the development of the nervous system, immature nerve cells receive signals from various molecules, proteins and cells. One class of molecule, cell adhesion molecules (CAMs), is particularly important in influencing nerve cells to extend their axons and find correct targets. Several CAMs, such as L1 and N-cadherin, have been shown to guide the growth of developing axons.

Dr. Vance Lemmon, formerly Professor of Neuroscience at Case Western Reserve University in Cleveland, Ohio, has been pursuing a thorough understanding of how L1 signals the nerve cells and influences their paths. Dr. Lemmon’s study provides a detailed biochemical explanation for how the movement of L1 is controlled within the nerve cells. Additionally, Drs. Ina Wanner and Patrick Wood conducted a study that describes how N-cadherin regulates the interactions between nerve fibers and the glial cells that support them. Dr. Wanner is now characterizing how developing glia cells pilot nerve fibers to their targets. She studies the role glial N-cadherin has in local guidance of growth cones by glia cells.

Nerve fibers are ultimately guided to their targets by chemical signals inside cells that result from interactions among CAMs and other growth factors. Another new Miami Project team member, Dr. John Bixby, studied one intracellular signaling protein, SHP-2, to learn its role in guiding cells to find their targets. When his lab inactivated SHP-2, they found that while the nerve fibers continued to grow and survive, they were unable to form normal branching patterns within their targets. This finding suggests that the SHP-2 signal has an important role in helping axons make appropriate connections. Further studies to identify and characterize the various molecular and cellular interactions that regulate axon guidance may lead to novel treatments for regeneration after injury.

Synopsis Publications

 Chen B, Hammonds-Odie L, Perron J, Masters BA, Bixby JL (2002) SHP-2 mediates target-regulated axonal termination and NGF-dependent neurite growth in sympathetic neurons. Dev Biol 252:170-187.

 Wanner IB, Wood PM (2002) N-Cadherin mediates axon-aligned process growth and cell-cell interaction in rat Schwann cells. J Neurosci 22:4066-4079.