Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Pathfinding by nerve growth cones depends on attractive and repulsive turning in response to a variety of guidance cues. Here we present direct evidence to demonstrate an essential and instructive role for microtubules (MTs) in growth cone steering. First, both growth cone attraction and repulsion induced by diffusible cues in culture can be completely blocked by low concentrations of drugs that specifically inhibit dynamic microtubule ends in the growth cone. Second, direct focal photoactivated release of the microtubule-stabilizing drug taxol on one side of the growth cone consistently induces attraction (turning toward the site of application). Using the focal pipette application method, we also show that local MT stabilization by taxol induces growth cone attraction, whereas local MT destabilization by the microtubule-disrupting drug nocodazole induces repulsion (turning away). Finally, the microtubule-initiated attractive turning requires the participation of the actin cytoskeleton: local microtubule stabilization induces preferential protrusion of lamellipodia before the attractive turning, and the attraction can be abolished by inhibition of either actin polymerization or the Rho family GTPases. Together, these results demonstrate a novel steering mechanism for growth cones in which local and selective modification of dynamic microtubules can initiate and instruct directional steering. With the subsequent concerted activity of the actin cytoskeleton, this microtubule-initiated mechanism provides the growth cone with the additional means to efficiently navigate through its environment.
Bentley,
Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment.
, Pubmed
Bentley,
Disoriented pathfinding by pioneer neurone growth cones deprived of filopodia by cytochalasin treatment.
,
Pubmed
Bentley,
Cytoskeletal events in growth cone steering.
1994,
Pubmed
Bradke,
The role of local actin instability in axon formation.
1999,
Pubmed
Challacombe,
Dynamic microtubule ends are required for growth cone turning to avoid an inhibitory guidance cue.
1997,
Pubmed
Chang,
Transport and turnover of microtubules in frog neurons depend on the pattern of axonal growth.
1998,
Pubmed
,
Xenbase
Chien,
Navigational errors made by growth cones without filopodia in the embryonic Xenopus brain.
1993,
Pubmed
,
Xenbase
Dent,
Axon branching requires interactions between dynamic microtubules and actin filaments.
2001,
Pubmed
Downing,
Structural basis for the interaction of tubulin with proteins and drugs that affect microtubule dynamics.
2000,
Pubmed
Díaz,
Molecular recognition of taxol by microtubules. Kinetics and thermodynamics of binding of fluorescent taxol derivatives to an exposed site.
2000,
Pubmed
Fukata,
Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170.
2002,
Pubmed
Gallo,
Involvement of microtubules in the regulation of neuronal growth cone morphologic remodeling.
1998,
Pubmed
Gundersen,
Microtubules and signal transduction.
1999,
Pubmed
Hall,
Rho GTPases and the actin cytoskeleton.
1998,
Pubmed
Jay,
Molecular mechanisms of directed growth cone motility.
1996,
Pubmed
Just,
Glucosylation of Rho proteins by Clostridium difficile toxin B.
1995,
Pubmed
Kennedy,
Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord.
1994,
Pubmed
Krendel,
Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton.
2002,
Pubmed
Lin,
Growth cone advance is inversely proportional to retrograde F-actin flow.
1995,
Pubmed
Lin,
Cytoskeletal reorganization underlying growth cone motility.
1994,
Pubmed
Lohof,
Asymmetric modulation of cytosolic cAMP activity induces growth cone turning.
1992,
Pubmed
,
Xenbase
Mack,
The microtubule-associated protein MAP1B is involved in local stabilization of turning growth cones.
2000,
Pubmed
Marsh,
Growth of neurites without filopodial or lamellipodial activity in the presence of cytochalasin B.
1984,
Pubmed
Mikhailov,
Relationship between microtubule dynamics and lamellipodium formation revealed by direct imaging of microtubules in cells treated with nocodazole or taxol.
1998,
Pubmed
Ming,
Electrical activity modulates growth cone guidance by diffusible factors.
2001,
Pubmed
,
Xenbase
Mitchison,
Cytoskeletal dynamics and nerve growth.
1988,
Pubmed
Parent,
A cell's sense of direction.
1999,
Pubmed
Pollard,
Molecular mechanisms controlling actin filament dynamics in nonmuscle cells.
2000,
Pubmed
Rochlin,
Polymerizing microtubules activate site-directed F-actin assembly in nerve growth cones.
1999,
Pubmed
Rochlin,
Microtubule stability decreases axon elongation but not axoplasm production.
1996,
Pubmed
Salmon,
Dual-wavelength fluorescent speckle microscopy reveals coupling of microtubule and actin movements in migrating cells.
2002,
Pubmed
Schaefer,
Filopodia and actin arcs guide the assembly and transport of two populations of microtubules with unique dynamic parameters in neuronal growth cones.
2002,
Pubmed
Smith,
Neuronal cytomechanics: the actin-based motility of growth cones.
1988,
Pubmed
Spitzer,
The development of the action potential mechanism of amphibian neurons isolated in culture.
1976,
Pubmed
,
Xenbase
Suter,
Substrate-cytoskeletal coupling as a mechanism for the regulation of growth cone motility and guidance.
2000,
Pubmed
Tanaka,
Microtubule behavior in the growth cones of living neurons during axon elongation.
1991,
Pubmed
,
Xenbase
Tanaka,
The role of microtubules in growth cone turning at substrate boundaries.
1995,
Pubmed
,
Xenbase
Tanaka,
The role of microtubule dynamics in growth cone motility and axonal growth.
1995,
Pubmed
,
Xenbase
Tessier-Lavigne,
The molecular biology of axon guidance.
1996,
Pubmed
Vega,
Microtubule function in morphological differentiation: growth zones and growth cones.
1997,
Pubmed
Wang,
cAMP-mediated regulation of neurotrophin-induced collapse of nerve growth cones.
1998,
Pubmed
,
Xenbase
Waterman-Storer,
Positive feedback interactions between microtubule and actin dynamics during cell motility.
1999,
Pubmed
Waterman-Storer,
Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts.
1999,
Pubmed
Williamson,
Microtubule reorganization is obligatory for growth cone turning.
1996,
Pubmed
Zheng,
Turning of nerve growth cones induced by localized increases in intracellular calcium ions.
2000,
Pubmed
,
Xenbase
Zheng,
Essential role of filopodia in chemotropic turning of nerve growth cone induced by a glutamate gradient.
1996,
Pubmed
,
Xenbase
Zheng,
Calcium and chemotropic turning of nerve growth cones.
1996,
Pubmed
,
Xenbase
