During development of the visual system, retinal ganglion cells (RGCs) require cell-cell adhesion molecules and extracellular matrix proteins for axon growth. In this study, we demonstrate that the classical cadherin, E-cadherin, is expressed in RGCs from E6 to E12 and promotes neurite outgrowth from all regions of the chick retina at E6, E8 and E10. E-cadherin is also expressed in the optic tectum. E-cadherin adhesion blocking antibodies specifically inhibit neurite outgrowth on an E-cadherin substrate. The receptor-type protein tyrosine phosphatase, PTPmu, associates with E-cadherin. In this manuscript, we demonstrate that antisense-mediated down-regulation of PTPmu, overexpression of catalytically inactive PTPmu and perturbation of endogenous PTPmu using a specific PTPmu inhibitor peptide results in a substantial reduction in neurite outgrowth on E-cadherin. Taken together, these findings demonstrate that E-cadherin is an important adhesion molecule for chick RGC neurite outgrowth and suggest that PTPmu expression and catalytic activity are required for outgrowth on an E-cadherin substrate.