N-cadherin function is required for differentiation-dependent cytoskeletalreorganization in lens cells in vitro

Members of the cadherin family of cell adhesion molecules participate in ca lcium-dependent cell-cell adhesions that are necessary for the cell sorting events that regulate early developmental processes. Although individual ca dherin molecules have been shown to participate in tissue histogenesis, the regulation of function of these receptors in cell differentiation has been more difficult to identify. We have determined that N-cadherin linkage to the cytoskeleton is correlated with lens cell differentiation in vivo. Thro ugh the use of a chick embryo lens culture system that mimics differentiati on in vivo, we have determined that N-cadherin linkage to the cytoskeleton is altered and lens differentiation is blocked by function-blocking antibod ies to N-cadherin, In the presence of the N-cadherin function-blocking anti body, NCD-2, both N-cadherin and filamentous actin are prevented from organ izing at the cortical membranes. This correlates with an inhibition of lens morphogenesis and differentiation. These results are paralleled by changes in the expression of the molecular components of the cadherin-catenin comp lex and their linkage to the actin cytoskeleton. In the presence of NCD-2, expression of N-cadherin, alpha-catenin, and beta-catenin is inhibited and their association with the cytoskeleton blocked, Overall cadherin expressio n, however, remains unchanged as demonstrated by studies with a pan-cadheri n antibody. This is accompanied by an increase in expression of the cadheri n cytoskeletal protein plakoglobin. Although the cells have tried to compen sate for the loss of N-cadherin by up-regulation of another cadherin(s) and plakoglobin, this is unable to compensate for N-cadherin function. The dat a strongly suggest that N-cadherin and its associated cytoskeleton play an important role in the differentiation process that leads to the formation o f the crystalline lens. (C) 2000 Academic Press.