N-CADHERIN IN NORMAL AND ABNORMAL BRAIN-DEVELOPMENT

The brain relies upon numerous morphoregulatory molecules to control c ell-cell interactions, cell migration and neurite extension. N-cadheri n, a calcium-dependent cell adhesion molecule, is essential for normal CNS development. Hemophilic binding of N-cadherin depends upon a spec ific conformation assumed by the molecule when it binds calcium. N-cad herin is a substrate for a specific zinc-dependent protease that may b e involved in the regulation of N-cadherin at the cell surface. The re liance of N-cadherin on two cations for proper function makes it a pot ential target for toxicants which act by replacing or modifying calciu m or zinc at ion-binding sites. Exposure of the developing brain to le ad, an ubiquitous toxicant known to interact with calcium, disturbs ne ural tube closure and subsequent maturation of the nervous system. Pre liminary data indicates that lead may induce these effects by direct i nteraction with N-cadherin. Numerous common toxicants, including metal s and solvents, also perturb cadherins a nd cause defective CNS develo pment. These data indicate that changes in the spatio-temporal express ion of cadherin can result in profound alterations in neural structure and function, and may underlie CNS malformations caused by numerous t oxic agents. (C) 1994 Inter Press, Inc.