Anti-CDH6 monoclonal antibody, clone FQS8405

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.

Classical cadherins are important cell adhesion molecules specifying and separating brain nuclei and developmental compartments. Cadherin-22 (Cdh22) belongs to type II subfamily of classical cadherins, and is expressed at the midbrain-hindbrain boundary during early embryogenesis. In Fgfr1 mutant mouse embryos, which have a disturbed midbrain-hindbrain border, Cdh22 is down-regulated. Here, we studied expression of Cdh22 in developing mouse brain in more detail and compared it to expression of related family members. This revealed both complementary and overlapping patterns of Cdh22, Cdh11, Cdh8, and Cdh6 expression in distinct regions of the forebrain and midbrain. We used a mutated allele of Cdh22 to study its function in brain development. Loss of Cdh22 caused reduced postnatal viability. Despite strong Cdh22 expression in the developing brain, we did not observe defects in compartmentalization or abnormalities in the midbrain and forebrain nuclei in Cdh22 mutants. This may be explained by functional redundancy between type II cadherins. Developmental Dynamics 240:1989-2001, 2011. (C) 2011 Wiley-Liss, Inc.