Controlling Axon Growth and Mapping in the Visual System

Inventors: Yoo-Shick Lim, Todd McLaughlin, and Dennis O'Leary
Potential Uses: Drug Discovery and Development, Neurodegenerative disorders, gene therapy, and cell therapy.

Identification of cofactor p75 that controls axon growth, including guidance and mapping

Axonal connections in the mature nervous system are extraordinarily precise. To develop this precision, axons respond to a complex environment of guidance cues as they pathfind and, once within their target, form an orderly set of connections.

Though axon guidance systems eventually link to the cytoskeleton, distinct families of guidance molecules and receptors likely interact at multiple points in their signaling pathways, from ligand binding to intramembrane interactions to cytoskeletal alterations. We utilized the developing mouse visual system to identify the unique interactions between distinct families of potential axon guidance molecules at the origin of signaling events: the axon membrane. From this research we identified that p75 acts as a signaling partner with ephrin to mediate the repellent effect of ephrin-A reverse signaling on RGC axons (upon binding EphAs) and that this signaling is required for appropriate retinotopic mapping. Other researchers have suggested that p75 may have similar roles in other developing neuronal systems. Taken together this discovery may prove useful for future cell or gene therapy for correction of neurodegenerative disorders.