1. Section of Neurobiology, Division of Biology, University of California at San Diego, La Jolla, California 92093, USA
2. Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
3. The Salk Institute for Biological Studies, La Jolla, California 92037, USA
4. These authors contributed equally to this work
5. Present address: Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai 100032, China

Correspondence to: Mu-ming Poo³ Correspondence and requests for materials should be addressed to M.-m.P. (e-mail: Email: mpoo@uclink.berkeley.edu) or G.-l.M. (e-mail: Email: gming@biomail.ucsd.edu).

Abstract

Pathfinding by growing axons in the developing nervous system may be guided by gradients of extracellular guidance factors. Analogous to the process of chemotaxis in microorganisms, we found that axonal growth cones of cultured Xenopus spinal neurons exhibit adaptation during chemotactic migration, undergoing consecutive phases of desensitization and resensitization in the presence of increasing basal concentrations of the guidance factor netrin-1 or brain-derived neurotrophic factor. The desensitization is specific to the guidance factor and is accompanied by a reduction of Ca²⁺ signalling, whereas resensitization requires activation of mitogen-associated protein kinase and local protein synthesis. Such adaptive behaviour allows the growth cone to re-adjust its sensitivity over a wide range of concentrations of the guidance factor, an essential feature for long-range chemotaxis.