Cadherin-13 Maintains Retinotectal Synapses via Trans-Neuronal Interactions

Maintaining precise synaptic contacts between neuronal partners is critical to ensure the proper functioning of the mammalian central nervous system (CNS). Diverse cell-recognition molecules, such as classic cadherins (Cdhs), are part of the molecular machinery mediating synaptic choices during development and synaptic maintenance. Yet, the principles governing neuron-neuron wiring across diverse CNS neuron types remain largely unknown. The retinotectal synapses, connections from the retinal ganglion cells (RGCs) to the superior collicular (SC) neurons, offer an ideal experimental system to reveal molecular logic underlying synaptic choices and formation. This is due to the retina's unidirectional and laminar-restricted projections to the SC and the large databases of presynaptic RGC subtypes and postsynaptic SC neuronal types. Here, we focused on determining the role of Type II Cdhs in wiring the retinotectal synapses. We surveyed Cdhs expression patterns at neuronal resolution and revealed that Cdh13 is enriched in the Wide-Field neurons in the superficial SC (sSC). In either the Cdh13 null mutant or selective adult deletion within the Wide-Field neurons, there is a significant reduction of spine densities in the distal dendrites of these neurons in both sexes. Additionally, Cdh13 removal from presynaptic RGCs reduced dendritic spines in the postsynaptic Wide-Field neurons. Cdh13-expressing RGCs use differential mechanisms than αRGCs and On-Off Direction-Selective Ganglion Cells (ooDSGCs) to form specific retinotectal synapses. The results revealed a selective trans-neuronal interaction mediated by Cdh13 to maintain proper retinotectal synapses in vivo . Significance Statement The Cadherin (Cdh) family of molecules is implicated in selective synaptic recognitions in intra-retinal circuits. However, their roles in wiring the rest of the CNS circuit remain to be explored. The retinotectal synapses represent an established model for understanding selective neural circuit wiring between diverse presynaptic and postsynaptic neuron types. We first showed that Cdh13 is enriched in restricted superior colliculus neurons. We found that a single Type II Cdh, Cdh13, allows cell-type-specific spine maintenance from the retina to the superior colliculus. These results shed light on how differential Cdh expression can direct cell-type specific wiring beyond the retina into the rest of the mammalian CNS. The cellular and molecular mechanisms established in this study m