Ig superfamily cell adhesion molecules in the brain

Cell adhesion molecules of the immunoglobulin superfamily (IgSF CAMs) were discovered 25 years ago based on their role in cell-cell adhesion. Ever since, they have played a major role in developmental neuroscience research. The elucidation of IgSF CAM structure and function has been tightly linked to the establishment of new areas of research. Over the years, our view of the role of the IgSF CAMs has changed. First, they were thought to provide "specific glue" segregating subtypes of cells in the nervous system. Soon it became clear that IgSF CAMs can do much more. The focus shifted from simple adhesion to CAM-associated signaling that was shown to be involved in the promotion of axon growth and the regulation of cell migration. From there it was a small step to axon guidance, a field that has been given a lot of attention during the last decade. More recently, the involvement of IgSF CAMs in synapse formation and maturation has been discovered, although this last step in the formation of neural circuits was thought to be the domain of other families of cell adhesion molecules, such as the neuroligins, the neurexins, and the cadherins. Certainly, the most striking discovery in the context of IgSF CAMs has been the diversity of signaling mechanisms that are associated with them. The versatility of signals and their complexity make IgSF CAMs a perfect tool for brain development.