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Journal of Neuroscience, Vol 16, 1140-1149, Copyright © 1996 by Society for Neuroscience
Essential role of filopodia in chemotropic turning of nerve growth cone induced by a glutamate gradient
JQ Zheng, JJ Wan and MM Poo
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Pathfinding of growing neurites depends on turning of the growth cone in
response to extracellular cues. Motile filopodia of the growth cone are
known to be critical for mediating contact-dependent guidance of the growth
cone. However, whether filopodia also play an essential role in growth cone
turning response induced by a diffusible chemotropic substance is unclear.
Growth cones of cultured Xenopus spinal neurons exhibited chemotropic
turning responses in a gradient of glutamate within a limited range of
concentrations. This turning response depends on the activation of the NMDA
subtype of glutamate receptors and requires the presence of extracellular
Ca2+. Time-lapse differential interference contrast microscopy with
quantitative analysis of filopodia dynamics showed a close correlation
between an increased number of filopodia on the side of the growth cone
facing the glutamate source and the turning. Such filopodia asymmetry was
observed within minutes after the onset of the glutamate gradient, before
any detectable turning of the growth cone. In Ca(2+)-free medium, no
filopodia asymmetry was induced by the glutamate gradient, and no growth
cone turning was observed. Furthermore, elimination of filopodia with a low
concentration of cytochalasin B completely abolished the turning response
without substantially affecting neurite extension. Thus, filopodia may be
required for chemotropic guidance of the growth cone, and an asymmetry in
filopodia distribution may be an early cellular event responsible for
determining the direction the growth cone advances.
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