Cadherins in embryonic and neural morphogenesis

Cadherins not only maintain the structural integrity of cells and tissues but also control a wide array of cellular behaviours. They are instrumental for cell and tissue polarization, and they regulate cell movements such as cell sorting, cell migration and cell rearrangements. Cadherins may also contribute to neurite outgrowth and pathfinding, and to synaptic specificity and modulation in the central nervous system. Key Points The cadherin superfamily is one of the main groups of adhesion molecules that mediate cell?cell adhesion in both vertebrates and invertebrates. This diverse superfamily, with over 300 vertebrate members, is defined by the presence of a cadherin domain. A classification of seven subfamilies is presented in this review, on the basis of the domain layout. A predominant function of cadherins is to mediate cell?cell interactions. Structural studies indicate that cadherins form cis dimers in a calcium-dependent manner. Cis dimers are presumably the building blocks for lateral clustering and for trans -dimer formation between cells. Classic cadherins mediate two types of adhesive contacts: diffuse adhesive contacts and ultrastructurally defined cell?cell adherens junctions. Diffuse adhesive contacts are probably formed by oligomerization of cadherin trans dimers. Invertebrate studies indicate that cadherins are not absolutely required for adherens junction formation. Cadherins are also important for forming and maintaining cell polarity in epithelial tissues. Here, they are proposed to mediate localization of the sec 6/8 complex, which in turn directs polarized delivery of molecular components to the membrane. In the fly, cadherins are implicated in mediating planar epithelial polarity. Evidence from both Drosophila and the chick highlight another function for cadherins in generating asymmetric tissue organization, by setting up anterior?posterior and left?right asymmetry, respectively. Cell movements that occur during development require dynamic changes in adhesive interactions. Experiments in Xenopus and Drosophila indicate that cadherins might mediate cell movement during gastrulation and oogenesis, respectively. Cadherins are implicated in central nervous system organization, neurite outgrowth, axon patterning and fasciculation. Later, they are proposed to function in adherens junctions at the synapse. They may be required here to mediate synaptic plasticity, perhaps by providing an adhesive code.