mGluR6 coordinates cone terminal targeting and synaptic layer assembly during human retinal development

prior to synaptogenesis disrupted cone pedicle architecture, leading to mislocalization of synaptic proteins including Bassoon, ELFN2, and TRPM1, and ultimately resulting in widening or duplication of the outer plexiform layer (OPL). In contrast, deletion after synapse formation did not alter OPL synapses or morphology, revealing a temporally restricted requirement for mGluR6 during circuit assembly. These findings uncover a previously unrecognized role for mGluR6 in coordinating cone terminal targeting and synaptic layer assembly during human retinal development and highlight the power of temporally controlled genetic manipulation in organoid systems to reveal species-specific mechanisms of neural circuit formation.