Protein tyrosine phosphatase-mu differentially regulates neurite outgrowth of nasal and temporal neurons in the retina.

Cell adhesion molecules play an important role in the development of the visual system. The receptor-type protein tyrosine phosphatase, PTPmu is a cell adhesion molecule that mediates cell aggregation and may signal in response to adhesion. PTPmu is expressed in the chick retina during development and promotes neurite outgrowth from retinal ganglion cell (RGC) axons in vitro (Burden-Gulley and Brady-Kalnay, 1999). The axons of RGC neurons form the optic nerve, which is the sole output from the retina to the optic tectum in the chick. In this study, we observed that PTPmu expression in RGC axons occurs as a step gradient, with temporal axons expressing the highest level of PTPmu. PTPmu expression in the optic tectum occurred as a smooth descending gradient from anterior to posterior regions during development. Because temporal RGC axons innervate anterior tectal regions, PTPmu may regulate the formation of topographic projections to the tectum. In agreement with this hypothesis, a differential response of RGC neurites to a PTPmu substrate was also observed: RGCs of temporal retina were unable to extend neurites on PTPmu compared with neurites of nasal retina. When given a choice between PTPmu and a second substrate, the growth cones of temporal neurites clustered at the PTPmu border and stalled, thus avoiding additional growth on the PTPmu substrate. In contrast, PTPmu was permissive for growth of nasal neurites. Finally, application of soluble PTPmu to retinal cultures resulted in the collapse of temporal but not nasal growth cones. Therefore, PTPmu may specifically signal to temporal RGC axons to cease their forward growth after reaching the anterior tectum, thus allowing for subsequent innervation of deeper tectal layers.