The receptor tyrosine phosphatase CRYP alpha promotes intraretinal axon growth

Retinal ganglion cell axons grow towards the optic fissure in close contact with the basal membrane, an excellent growth substratum. One of the ligand s of receptor tyrosine phosphatase CRYP alpha is located on the retinal and tectal basal membranes. To analyze the role of this RPTP and its ligand in intraretinal growth and guidance of ganglion cell axons, we disrupted liga nd-receptor interactions on the retinal basal membrane in culture. Antibodi es against CRYP alpha strongly reduced retinal axon growth on the basal mem brane, and induced a dramatic change in morphology of retinal growth cones, reducing the size of growth cone lamellipodia. A similar effect was observ ed by blocking the ligand with a CRYP alpha ectodomain fusion protein. Thes e effects did not occur, or were much reduced, when axons were grown either on laminin-1, on matrigel or on basal membranes with glial endfeet removed . This indicates that a ligand for CRYP alpha is located on glial endfeet. These results show for the first time in vertebrates that the interaction o f a receptor tyrosine phosphatase with its ligand is crucial not only for p romotion of retinal axon growth but also for maintenance of retinal growth cone lamellipodia on basal membranes.