Cadherin-6 Mediates Axon-Target Matching in a Non-Image-Forming Visual Circuit

• Published in: Neuron (Cambridge, Mass.) Vol. 71; no. 4; pp. 632 - 639
• Main Authors: Osterhout, Jessica A., Josten, Nicko, Yamada, Jena, Pan, Feng, Wu, Shaw-wen, Nguyen, Phong L., Panagiotakos, Georgia, Inoue, Yukiko U., Egusa, Saki F., Volgyi, Bela, Inoue, Takayoshi, Bloomfield, Stewart A., Barres, Ben A., Berson, David M., Feldheim, David A., Huberman, Andrew D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.08.2011; Elsevier Limited
• Subjects: Animals; Axons - physiology; Axons - ultrastructure; Brain; Cadherins - genetics; Cadherins - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Insects; Mice; Mice, Knockout; Nerve Net - anatomy & histology; Nerve Net - physiology; Neurons; Photoreceptors; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - physiology; Rodents; Target recognition; Visual Cortex - anatomy & histology; Visual Cortex - physiology; Visual Pathways - anatomy & histology; Visual Pathways - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2011.07.006

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. ► A molecular signature for a functionally specialized visual circuit in mammals ► Specific cadherins in a subset of retinal cells and their targets in the brain ► Cadherins ensure proper connections between specific retinal cells and their targets ► A potential general mechanism for axon-target specificity in mammals