Multiple functions for the cadherin/catenin complex during neuronal development.

Abstract

The cadherin/catenin complex is a major transmembrane signaling complex through which extracellular signals can influence the cytoskeleton. It is present in neuronal processes during early development (J. Neurosci. 18 (1998) 6892) and appears to play multiple roles during neural circuit formation and maturation (Nat. Neurosci. 7 (2004) 357; Neuron 35 (2002) 77; Nat. Neurosci. 6 (2003) 1169). In previous work (Nat. Neurosci. 6 (2003) 1169), we showed that molecular manipulation of the cadherin/catenin complex has significant effects on the dendritic aborization of cultured hippocampal neurons at 9 days in vitro (d.i.v.). Here we extend these observations by examining the effects of over-expression of beta-catenin (fused to GFP; GFP-beta-cat(*)) or sequestering endogenous beta-catenin [using the intracellular domain of N-cadherin; Ncad(intra)] in cultured hippocampal neurons at different developmental stages. When transfected at 1 d.i.v. and assayed 48 h later, over-expression of GFP-beta-cat(*) increased axonal length and complexity, while sequestering endogenous beta-catenin had the opposite effect. Dendritic aborization was also enhanced by GFP-beta-cat(*) expression throughout early development although the magnitude of this effect decreased as neurons matured from 3 to 12 d.i.v. Finally, at 12 d.i.v., GFP-beta-cat(*) expression increased the density of dendritic spines although not the relative proportion of different subtypes of spines. These results demonstrate that the cadherin/catenin complex plays multiple roles in the development of neuronal morphology and that these roles change as neurons mature.