Direct evidence that growth cones pull

Abstract

THERE is controversy over whether axonal elongation is the result of a pulling growth cone and the role of tension in axonal elongation^l-4. Earlier in this decade, the consensus was that axons or neurites elongated from tension generated by forward motility of the growth cone^5,6. It was presumed that contractile filopodia were the source of the tension moving the growth cone^7,8. But this view was challenged by experiments showing that neurites elongate, albeit abnormally, in the presence of cytochalasin, which inhibits growth-cone and filopodial movements⁹. Additionally, high resol-ution, video-enhanced observations of growth-cone activity argued against filopodial shortening as a source of tension, suggesting instead that an extrusion of cytoplasm rather than a pulling process, is the key event in neurite elongation^1,3. Studies of slow axonal transport¹⁰, however, indicate that much slower cytoskeletal pushing underlies axonal elongation. We report here direct measurements of neurite force as a function of growth-cone advance which show that they are linearly related and accompanied by apparent neurite growth. No increase in force occurs in neurites whose growth cone fails to advance.