Microtubules + actin in growth cones from Suh et al., J. Neuroscience 2004

During development, axons are guided along specific pathways in the embryo by multiple families of axon guidance molecules. These molecules are expressed by cells along developing pathways and activate guidance receptors on axon growth cones. Receptor activation leads to signaling pathways that ultimately regulate the assembly and disassembly of cytoskeletal elements to govern the direction of axon growth. (Download Publications) (View movies of growth cones)

In recent years, it has become increasingly appreciated that the expression of axon guidance molecules is not limited only to the developmental period during which the basic pattern of neuronal connectivity is established. It is also clear that guidance molecules re-appear in the context of neuronal injury and are expressed by various cells around sites of spinal cord damage. The exact roles of these guidance molecules in CNS injury are not fully understood but have been proposed to include inhibition of CNS axon regeneration and the re-organization of cellular architecture as a consequence of injury. Our laboratory is investigating the repertoire of guidance molecules expressed in the adult optic nerve after injury.Recent work demonstrated that members of the EphB family of receptor tyrosine kinases, previously known for their role in embryonic retinal axonal guidance, reappears in the setting of adult optic nerve injury (Liu et al. 2006). Results from studies using a combination of in vitro axon assays and analysis of EphB3 mutant mice, showed that EphB3 functions as an endogenous mediator of adult retinal axon sprouting after traumatic injury.

A current focus of the laboratory is whether potential ‘guidance molecules’ also play a role in other forms of axon injury, such as chronic progressive optic neuropathies including glaucomatous retinal axon damage. Glaucoma is the leading cause of irreversible blindness in the world and is characterized by axon damage that is thought to originate at the optic nerve head, which then ultimately leads to retinal ganglion cell death and loss of vision. Recent results in animal models of glaucoma showed that EphB molecules are specifically upregulated in their expression at the optic nerve head around the time of onset of retinal axon loss (Du et al., in press). Ongoing studies explore the potential functions of EphB molecules and their ligands the ephrins in the development of disease.

Retinal ganglion cell axon sprouting after optic nerve injury.