Growth cone responses to growth and chemotropic factors

During nervous system development axons reach their target areas under the influence of numerous guidance cues that affect rate and direction of growth. This report addresses the unsettled question of whether and to what extent growth velocity and turning responses (attraction, repulsion) are interdependent. We exposed individual growth cones of fetal rat dorsal root ganglion neurons in culture asymmetrically to gradients of seven different factors and recorded their growth rates and turning angles. Growth cones exhibited divergent patterns of turning and growth responses. For example, hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1) and thrombin all promoted growth, but HGF was a powerful attractant, thrombin a potent repellent and IGF-1 did not elicit turning. Galanin and neuropeptide Y also affected growth and/or turning differentially. Finally, nerve growth factor in the culture medium not only inhibited the turning responses to HGF, but also converted growth promotion of HGF and IGF-1 into inhibition. Overall, our studies indicate that: (i) turning and advance are regulated independently, except that strong attractive or repulsive responses generally are accompanied by growth promotion; (ii) asymmetric growth factor application per se does not elicit attraction; (iii) regulation of the two parameters may occur through a single receptor; and (iv) the effects of combined growth factors may not be additive and can be inhibitory.