Retinotectal ligands for the receptor tyrosine phosphatase CRYPalpha

The cell adhesion molecule-like tyrosine phosphatase CRYPalpha is localized on retinal axons and their growth cones. We present evidence that two isoforms of this type IIa phosphatase, CRYPalpha1 and CRYPalpha2, have extracellular ligands along the developing retinotectal pathway. Using alkaline phosphatase fusion proteins containing the CRYPalpha1 ectodomain, we detect a prominent ligand on basement membranes of the early retina, optic stalk, and chiasm. A second ligand is observed in the endfeet region of radial processes in the developing stratum opticum, the site of initial retinal axon invasion. This latter ligand binds CRYPalpha2 preferentially. Further ligand interactions are detected for both CRYPalpha protein isoforms in retinorecipient tectal laminae and on retinal fibers themselves. CRYPalpha thus has cell- and matrix-associated ligands along the entire retinotectal projection. Moreover, these ligands appear to be heterotypic and interact with CRYPalpha through both its immunoglobulin and fibronectin type III regions. The anteroposterior levels of the ligands are relatively uniform within the retina and tectum, suggesting that the CRYPalpha protein within retinal axons does not directly recognise topographically graded guidance cues. We propose that CRYPalpha may have a permissive role in promoting retinal axon growth across the eye and tectum and that its functions are modulated temporally and spatially by isoform-specific interactions with cell- and matrix-associated ligands.