N-cadherin negatively regulates collective Drosophila glial migration via actin cytoskeleton remodeling

Abstract

Cell migration is an essential and highly regulated process. During development, glia and neurons migrate over long distances, in most cases collectively, to reach their final destination and build the sophisticated architecture of the nervous system, the most complex tissue of the body. Collective migration is highly stereotyped and efficient, defects in the process leading to severe human diseases that include mental retardation. This dynamic process entails extensive cell communication and coordination, hence the real challenge is to analyze it in the whole organism and at cellular resolution. We here investigate the impact of the N-cadherin adhesion molecule on collective glial migration using the Drosophila developing wing and cell-type specific manipulation of gene expression. We show that N-cadherin timely accumulates in glial cells and that its levels affect migration efficiency. N-cadherin works as a molecular brake in a dosage dependent manner by negatively controlling actin nucleation and cytoskeleton remodeling through α/β catenins. This is the first in vivo evidence for N-cadherin negatively and cell autonomously controlling collective migration.