The Netrin family of guidance factors: emphasis on Netrin-1 signalling

Abstract

During the development of the nervous system, neurons respond to the coordinated action of a variety of attractive and repulsive signals from the embryonic environment. Netrins form a family of extracellular proteins that regulate the migration of neurons and axonal growth cones. These proteins are bifunctional signals that are chemoattractive for some neurons and chemorepellent for others. Netrins mainly interact with the specific receptors DCC and UNC-5 family. To date, several Netrins have been described in mouse and humans: Netrin-1, -3/NTL2, -4/beta and G-Netrins. Netrin-1 is the most studied member of the family. It is involved in the development many projections of the nervous system. When Netrin-1 interacts with its specific receptors, a cascade of local cytoplasmic events is triggered. Several signal transduction pathways and effector molecules have been implicated in the response to Netrin-1: small Rho-GTPases, MAP-Kinases, second messengers and the Microtubule Associated Protein 1B (MAP1B).