Expression and adhesion profiles of SynCAM molecules indicate distinct neuronal functions

Abstract

Cell-cell interactions through adhesion molecules play key roles in the development of the nervous system. Synaptic cell adhesion molecules (SynCAMs) comprise a group of four immunoglobulin (Ig) superfamily members that mediate adhesion and are prominently expressed in the brain. Although SynCAMs have been implicated in the differentiation of neurons, there has been no comprehensive analysis of their expression patterns. Here we examine the spatiotemporal expression patterns of SynCAMs by using reverse transcriptase-polymerase chain reaction, in situ hybridization, and immunohistological techniques. SynCAMs 1-4 are widely expressed throughout the developing and adult central nervous system. They are prominently expressed in neurons throughout the brain and are present in both excitatory and inhibitory neurons. Investigation of different brain regions in the developing and mature mouse brain indicates that each SynCAM exhibits a distinct spatiotemporal expression pattern. This is observed in all regions analyzed and is particularly notable in the cerebellum, where SynCAMs display highly distinct expression in cerebellar granule and Purkinje cells. These unique expression profiles are complemented by specific heterophilic adhesion patterns of SynCAM family members, as shown by cell overlay experiments. Three prominent interactions are observed, mediated by the extracellular domains of SynCAMs 1/2, 2/4, and 3/4. These expression and adhesion profiles of SynCAMs together with their previously reported functions in synapse organization indicate that SynCAM proteins contribute importantly to the synaptic circuitry of the central nervous system.