Cell adhesion molecules during inner ear and hair cell development, including Notch and its ligands

The vertebrate inner ear develops from a population of placodally derived epithelial cells that initially invaginate to form the otocyst. As development continues, subsets of cells within this population become specified to develop as specific structures within the ear. Subsequently, individual cells undergo morphogenetic and differentiative changes related to the development of specific regions of the ear. The factors that regulate the different developmental events that are required for formation of a complete inner ear are still not completely understood. However, there is growing evidence to suggest that cell-cell adhesion and cell adhesion molecules may play key roles in several aspects of inner ear development. This chapter summarizes the molecular attributes of the known families of cell adhesion molecules and reviews the existing knowledge about the role of cell adhesion in inner ear development. The roles of cell adhesion in regionalization of the otocyst, cellular differentiation, and neurite extension are reviewed. In addition, the recently demonstrated role of a subset of adhesion molecules, although not necessarily cell-cell adhesion itself, in the development and orientation of hair cell stereociliary bundles is discussed. The role of adhesion molecules in stereociliary bundle development is even more intriguing in light of the fact that many of these molecules were identified as genetic mutations that lead to non-syndromic forms of deafness. These results highlight the importance of adhesion molecules in inner ear development and suggest that the developmental challenges that exist within the inner ear may have resulted in the development of novel functions for adhesion molecules. © 2003 Elsevier Inc. All rights reserved.