Target attraction: are developing axons guided by chemotropism?

Abstract

A century has elapsed since Ramón y Cajal proposed his chemotropic theory of axon guidance, i.e. the attraction of developing axons by diffusible molecules emanating from their targets. Although the precise contribution of axonal chemoattractants to guidance in vivo remains to be established, two lines of investigation have provided evidence for their existence and importance. First, concentration gradients of nerve growth factor (NGF) have been shown to orient the growth of regenerating sensory axons in vitro. Although NGF does not appear to guide axons during development, these studies show that growth cones can orient in gradients of diffusible molecules. Second, the cellular targets of several different classes of developing neurons have been shown to secrete as yet unidentified diffusible factors that can orient axons. We review these studies and discuss the potential contribution of chemotropism to the establishment of axonal projection patterns in vertebrates.