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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptation, Biological* / drug effects
-
Animals
-
Brain-Derived Neurotrophic Factor / pharmacology
-
Calcium Signaling / drug effects
-
Cell Size / drug effects
-
Chemotaxis* / drug effects
-
Chick Embryo
-
Enzyme Activation / drug effects
-
Growth Cones / drug effects
-
Growth Cones / enzymology
-
Growth Cones / physiology*
-
Mitogen-Activated Protein Kinases / metabolism
-
Nerve Growth Factors / metabolism
-
Nerve Growth Factors / pharmacology
-
Netrin Receptors
-
Netrin-1
-
Protein Synthesis Inhibitors / pharmacology
-
Receptors, Cell Surface / metabolism
-
Spinal Cord / cytology
-
Spinal Cord / embryology
-
Tumor Suppressor Proteins
-
Xenopus / embryology
-
Xenopus / physiology
Substances
-
Brain-Derived Neurotrophic Factor
-
Nerve Growth Factors
-
Netrin Receptors
-
Protein Synthesis Inhibitors
-
Receptors, Cell Surface
-
Tumor Suppressor Proteins
-
Netrin-1
-
Mitogen-Activated Protein Kinases