Classic cadherins regulate tangential migration of precerebellar neurons in the caudal hindbrain

Abstract

Classic cadherins are calcium dependent homophilic cell adhesion molecules that play a key role in developmental processes such as morphogenesis, compartmentalization and maintenance of a tissue. They also play important roles in development and function of the nervous system. Although classic cadherins have been shown to be involved in the migration of non-neuronal cells, little is known about their role in neuronal migration. Here, we show that classic cadherins are essential for the migration of precerebellar neurons. In situ hybridization analysis shows that at least four classic cadherins, cadherin 6 (Cad6), cadherin 8 (Cad8), cadherin11 (Cad11) and N-cadherin (Ncad), are expressed in the migratory streams of lateral reticular nucleus and external cuneate nucleus (LRN/ECN) neurons. Functional analysis performed by electroporation of cadherin constructs into the hindbrain indicates requirement for cadherins in the migration of LRN/ECN neurons both in vitro and in vivo. While overexpression of full-length classic cadherins, NCAD and CAD11, has no effect on LRN/ECN neuron migration, overexpression of two dominant negative (DN) constructs, membrane-bound form and cytoplasmic form, slows it down. Introduction of a DN construct does not alter some characteristics of LRN/ECN cells as indicated by a molecular marker, TAG1, and their responsiveness to chemotropic activity of the floor plate (FP). These results suggest that classic cadherins contribute to contact-dependent mechanisms of precerebellar neuron migration probably via their adhesive property.