Neural cell adhesion molecules of the immunoglobulin superfamily: role in axon growth and guidance.

NCAM, L1, and DCC--immunoglobulin cell adhesion molecules (Ig CAMs)--are widely expressed during development. Many workers have dismissed a role for such molecules in the control of axonal growth and guidance because they do not show highly restricted expression patterns. Yet evidence from a number of model systems suggests all three CAMs play a role in the development of specific projections in the nervous system. For example, there is a reduction in mossy fiber tracts in the hippocampus of mice that lack NCAM, a requirement for DCC in the response of commissural neurons to a floor plate-derived chemoattractant, and a loss of corticospinal tracts in humans who carry mutations in the L1 gene. The above paradox might be explained by the observation that differential post-translational processing can modulate CAMs function and that alternative splicing can generate functionally distinct isoforms of a CAM. Activation of the FGF tyrosine kinase receptor is required for the responses stimulated by NCAM and L1, and the importance of regulated tyrosine phosphorylation for growth and guidance is underscored by the involvement of receptor tyrosine phosphatases in this process.