Intercellular adhesion in morphogenesis: molecular and biophysical considerations.

A major challenge in developmental biology is to understand how cellular processes that result from expression of the genetic program determine the material properties and shape transformations of tissues during morphogenesis. Cell/cell adhesion is critical in development, and it controls many aspects of tissue rearrangements that support morphogenesis. Intercellular adhesion not only allows cells to adhere together but also supports structure and function compartmentalization on the scale of cell assemblies, tissues, and organs. In metazoans, cadherins comprise a major class of cell/cell adhesion proteins. They form Ca(2+)-dependent, homophilic adhesive contacts between neighboring cells that results in remodeling of the underlying cortical cytoskeleton with consequential changes in mechanical properties of cells. During development, programmed cues modulate cadherin levels and subtype expression, and downstream signaling to the cortical cytoskeleton resulting in a wide continuum of adhesive properties. A quantitative output from cell/cell adhesion is intercellular adhesion energy, which as a critical determinant of cell shape and position within the tissue, and tissue shape and position in the organism. We discuss molecular mechanisms underlying intercellular adhesion energy and its role in tissue morphogenesis.