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. Earlier in this decade, the consensus was that axons or neurites elongated from tension generated by forward motility of the growth cone. It was presumed that contractile filopodia were the source of the tension moving the growth cone. But this view was challenged by experiments showing that neurites elongate, albeit abnormally, in the presence of cytochalasin, which inhibits growth-cone and filopodial movements. Additionally, high resolution, 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. Studies of slow axonal transport, 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.