The Cdh6-expressing targets relate to circadian rhythm entrainment (vLGN and IGL) (Harrington, 1997), pupil constriction (OPN) (Güler et al., 2008) and oculomotor

functions (mdPPN) (Giolli et al., 2006). Cdh6 expression was specific to selleck screening library these targets during late embryonic and early postnatal development (∼E18–P4), the stage when RGC axons innervate their targets (Godement et al., 1984) with Cdh6 expression persisting into the first postnatal week (Figure 1). The other cadherins we assayed showed patterns of expression that were notably different from Cdh6. Cdh1, 3, 4, 5, 7, and 8 were not expressed by the OPN or mdPPN although Cdh4, 7, and 8 were expressed by other retinorecipient nuclei (Figures 1H, 1J, 1K, 1L, 1N, and 1O and unpublished observations). Indeed, Cdh4 and Cdh8 were expressed by regions adjacent to and surrounding the OPN, but were see more absent from the OPN itself (Figures 1K and

1O). Of the cadherins we assayed, only one of them, Cdh2, was expressed by the OPN during early postnatal development, but Cdh2 was expressed by all other retinorecipient areas too (Figure 1I; data not shown). Thus, during the developmental stage when RGC axons select their targets in the brain, the adhesion molecule Cdh6 is selectively expressed by a subset of non-image-forming retinorecipient targets. To examine whether Cdh6 plays a functional role in retinofugal targeting, we needed a way to visualize the axons of the particular RGCs that innervate Cdh6 expressing visual targets. We screened a library of BAC transgenic mice Rutecarpine (Gong et al., 2003) and found that Cdh3-GFP mice selectively label the RGCs that innervate Cdh6 expressing targets (Figure 2 and see Figure S1 available online). We injected CTb-594 into both eyes of Cdh3-GFP mice (ages P0–P20) and then examined each of those targets for the axons of Cdh3-GFP RGCs (hereafter referred to as Cdh3-RGCs). Cdh3-RGC axons terminated in the vLGN and IGL, whereas the adjacent dLGN, the target that relays visual information to the cortex for image perception, was virtually devoid of Cdh3-RGC axons (Figures 2A–2E and S1). Cdh3-RGC axons also densely innervated the OPN (Figures 2A,

2B, 2F–2I, and S1) specifically in the OPN “core,” whereas the OPN “shell” was devoid of Cdh3-RGC axons (Figures 2H and 2I). A limited number of Cdh3-RGC axons remained in the optic tract until they arrived to the caudal pretectum, wherein they terminated in two dense foci corresponding to the mdPPN (Figures 2J and 2K; Scalia, 1972). We are confident the GFP axons observed in the vLGN, IGL, OPN, and mdPPN originated from RGCs because they disappeared from those targets following eye removal (not shown). Indeed, with the exception of olfactory glia, a subset of brainstem nuclei and a small population of cells near the fourth ventricle, the brains of Cdh3-GFP mice were remarkably devoid of GFP-expressing cells (Figures 2A, 2B, S1, and S2).