Cadherin-6 mediates axon-target matching in a non-image-forming visual circuit.

Neural circuits consist of highly precise connections among specific types of neurons that serve a common functional goal. How neurons distinguish among different synaptic targets to form functionally precise circuits remains largely unknown. Here, we show that during development, the adhesion molecule cadherin-6 (Cdh6) is expressed by a subset of retinal ganglion cells (RGCs) and also by their targets in the brain. All of the Cdh6-expressing retinorecipient nuclei mediate non-image-forming visual functions. A screen of mice expressing GFP in specific subsets of RGCs revealed that Cdh3-RGCs which also express Cdh6 selectively innervate Cdh6-expressing retinorecipient targets. Moreover, in Cdh6-deficient mice, the axons of Cdh3-RGCs fail to properly innervate their targets and instead project to other visual nuclei. These findings provide functional evidence that classical cadherins promote mammalian CNS circuit development by ensuring that axons of specific cell types connect to their appropriate synaptic targets.

Milestones and mechanisms for generating specific synaptic connections between the eyes and the brain.

All information about the visual world is conveyed to the brain by a single type of neurons at the back of the eye called retinal ganglion cells (RGCs). Understanding how RGC axons locate and wire up with their targets is therefore critical to understanding visual development. In recent years, several important technological and conceptual advances have been made in this area, and yet, many fundamental questions remain unanswered. Indeed, while much is now known about how RGC axons pathfind at the optic chiasm and form retinotopic maps within their targets, how RGCs select their overall targets in the first place is poorly understood. Moreover, the signals that direct mammalian RGC axons to their appropriate layer within those targets remain unknown. The recent advent of genetic tools to selectively label and manipulate defined groups of RGCs is starting to provide a way to resolve these and other important questions about RGC wiring specificity. This field is therefore positioned to reveal new principles of visual circuit development that no doubt will extend to other regions of the CNS.