The cadherin superfamily in neuronal connections and interactions

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Abstract
The organization of neuronal circuits involves a number of processes that require cell–cell recognition and contacts. Cadherins are a family of cell–cell adhesion molecules comprising more than 100 members in vertebrates, which are grouped into subfamilies including classic cadherins, Flamingo/CELSRs and protocadherins, and are thought to have roles in various steps of neuronal cell interactions. N-cadherin and other vertebrate classic cadherins are essential not only for early morphogenesis of neural tissues but also for correct axon migration towards target areas, and for the extension of neuronal dendrites. Drosophila melanogaster N-cadherin (DN-cadherin) has been shown to be crucial for the formation of axonal connections with target neurons in both the visual and olfactory systems, and also for confining dendritic arborizations to specific glomeruli in these systems. The activity of DN-cadherin during the axon targeting seems to be controlled by cytoplasmic proteins including leukocyte antigen-related-receptor protein tyrosine phosphatase (LAR). Flamingo, a seven-pass transmembrane cadherin, is required for the correct targeting of retinal axons in visual circuits in D. melanogaster. A vertebrate homologue of Flamingo, CELSR2, regulates dendritic arbor patterning in the cerebellum, and another homologue, CELSR3, is important for axon tract formation. Some protocadherins, which show a large diversification due to a unique gene organization, seem to be involved in synapse formation and neuronal survival. However, the biological roles of this subfamily remain largely unknown. In conclusion, members of the cadherin superfamily control axon–target recognition and connections, as well as other types of neuronal interactions in a subfamily-specific manner.