Mechanisms and molecules that control growth cone guidance

Neuronal growth cones traverse long distances along appropriate pathways to find their correct targets. This review presents an overview of the mechanisms and molecules that control these events. Secreted and cell surface ligands in the growth cone's environment bind to receptors on the growth cone's surface, trigger second-messenger signals, and lead to appropriate steering decisions. Growth cones appear to be guided by at least four different mechanisms: contact-mediated attraction, chemoattraction, contact-mediated repulsion, and chemorepulsion. These mechanisms are mediated by many different families of guidance molecules, including neural cell adhesion molecules of the immunoglobulin superfamily, netrins, and semaphorins, all of which appear to be highly conserved from worms and fruitflies to mice and humans. We are just beginning to gain insights into the functions of these and other molecules in the developing organism by the use of genetic analysis.