βII-spectrin is required for synaptic positioning during retinal development

Neural circuit assembly is a multi-step process where synaptic partners are often born at distinct developmental stages, and yet they must find each other and form precise synaptic connections with one another. This developmental process often relies on late-born neurons extending their processes to the appropriate layer to find and make synaptic connections to their early-born targets. The molecular mechanism responsible for the integration of late-born neurons into an emerging neural circuit remains unclear. Here we uncovered a new role for the cytoskeletal protein βII-spectrin in properly positioning pre- and post-synaptic neurons to the developing synaptic layer. Loss of βII-spectrin disrupts retinal lamination, leads to synaptic connectivity defects, and results in impaired visual function. Together, these findings highlight a new function of βII-spectrin in assembling neural circuits in the mouse outer retina. Highlights Established a new role for βII-spectrin in assembling retinal circuits βII-spectrin positions pre- and post-synaptic neurons to the developing synaptic layer Early positioning of processes to the OPL is required for synaptogenesis Loss of βII-spectrin disrupts synaptic connectivity and impairs visual function