PTPμ expression and catalytic activity are required for PTPμ-mediated neurite outgrowth and repulsion

Cell adhesion molecules (CAMs) regulate neural development via both homophilic and heterophilic binding interactions. Various members of the receptor protein tyrosine phosphatase (RPTP) subfamily of CAMs mediate neurite outgrowth, yet in many cases, their ligands remain unknown. However, the PTPμ subfamily members are homophilic binding proteins. PTPμ is a growth-permissive substrate for nasal retinal ganglion cell (RGC) neurites and a growth inhibitory substrate for temporal RGC neurites. Whether PTPμ regulates these distinct behaviors via homophilic or heterophilic binding interactions is not currently known. In this manuscript, we demonstrate that PTPμ influences RGC axon guidance behaviors only in the E8 retina and not earlier in development. In addition, we demonstrate that PTPμ is permissive only for neurites from ventral-nasal retina and is repulsive to neurites from all other retinal quadrants. Furthermore, we show that PTPμ-mediated nasal neurite outgrowth and temporal repulsion require PTPμ expression and catalytic activity. These results are consistent with PTPμ homophilic binding generating a tyrosine phosphatase-dependent signal that ultimately leads to axon outgrowth or repulsion and that PTPμ's role in regulating axon guidance may be tightly regulated developmentally. In summary, these data demonstrate that PTPμ expression and catalytic activity are important in vertebrate axon guidance.