Protein tyrosine phosphatase receptor type kappa (PTPRκ) regulates Superior ON-Direction Selective Ganglion Cell development, facilitating image stabilization

In vertebrates, gaze stabilization during global visual motion requires ON direction-selective ganglion cells (oDSGCs) in the Accessory Optic System (AOS) to drive the optokinetic reflex (OKR). Three types of oDSGCs form independent mosaics; however, the mechanisms that specify and maintain their numbers to create these mosaics during development remain unknown. Here, we identify protein tyrosine phosphatase receptor type kappa (Ptprk) as a key regulator of Superior oDSGC density, the subtype tuned to upward motion. High-depth single-cell RNA sequencing (scRNAseq) reveals that Ptprk is selectively enriched in Superior oDSGCs compared to Inferior oDSGCs, which detect downward motion. Genetic deletion of Ptprk selectively halves the number of Superior oDSGCs while preserving the number of Inferior oDSGCs. Anatomically, Superior oDSGCs in Ptprk mutants exhibit compensatory neurite remodeling to preserve mosaics. Physiologically, oDSGCs have broader tuning curves, and a subset of Superior oDSGCS have aberrant preferred directions in Ptprk mutants. Postsynaptically, loss of Ptprk reduces oDSGC connectivity to central targets. Behaviorally, the OKR responses to upward motion are attenuated in both global and pan-retinal Ptprk mutants, confirming a retinal role for Ptprk in upward image stabilization. Together, these findings demonstrate that the density of a retinal ganglion cell type is under molecular control, and that reducing density drives neurite remodeling, alters circuit computation, and ultimately impairs visually-guided behavior.