N-cadherin-mediated adhesion and signaling from development to disease: lessons from mice

Of the 20 classical cadherin subtypes identified in mammals, the functions of the two initially identified family members E- (epithelial) and N- (neural) cadherin have been most extensively studied. E- and N-Cadherin have mostly mutually exclusive expression patterns, with E-cadherin expressed primarily in epithelial cells, whereas N-cadherin is found in a variety of cells, including neural, muscle, and mesenchymal cells. N-Cadherin function, in particular, appears to be cell context-dependent, as it can mediate strong cell-cell adhesion in the heart but induces changes in cell behavior in favor of a migratory phenotype in the context of epithelial-mesenchymal transition (EMT). The ability of tumor cells to alter their cadherin expression profile, for example, E- to N-cadherin, is critical for malignant progression. Recent advances in mouse molecular genetics, and specifically tissue-specific knockout and knockin alleles of N-cadherin, have provided some unexpected results. This chapter highlights some of the genetic studies that explored the complex role of N-cadherin in embryonic development and disease.