Protein Tyrosine Phosphatase-μ Differentially Regulates Neurite Outgrowth of Nasal and Temporal Neurons in the Retina

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Abstract
Cell adhesion molecules play an important role in the development of the visual system. The receptor-type protein tyrosine phosphatase, PTPμ, is a cell adhesion molecule that mediates cell aggregation and may signal in response to adhesion. PTPμ 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 PTPμ expression in RGC axons occurs as a step gradient, with temporal axons expressing the highest level of PTPμ. PTPμ 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, PTPμ may regulate the formation of topographic projections to the tectum. In agreement with this hypothesis, a differential response of RGC neurites to a PTPμ substrate was also observed: RGCs of temporal retina were unable to extend neurites on PTPμ compared with neurites of nasal retina. When given a choice between PTPμ and a second substrate, the growth cones of temporal neurites clustered at the PTPμ border and stalled, thus avoiding additional growth on the PTPμ substrate. In contrast, PTPμ was permissive for growth of nasal neurites. Finally, application of soluble PTPμ to retinal cultures resulted in the collapse of temporal but not nasal growth cones. Therefore, PTPμ 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.