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.

Deflection induced cellular focal adhesion and anisotropic growth on vertically aligned silicon nanowires with differing elasticity

“…The rate of neurite elongation is a linear function of pulling tension, provided either by the growth cone 43 or by experimental manipulation. 44 Furthermore, Lamoureux et al reported that mechanical tension using calibrated glass needles can break symmetry in neurons, and thereby specify which process becomes the axon.…”

Stochastic models of intracellular transport

“…Axonal elongation and cellular length control During neural development, the formation of synapses involves the elongation of an axon of one cell to locate the dendrites of another cell. Axon elongation is a consequence of the interplay between force generation at the growth cone that pulls the axon forward, pushing forces due to microtubule and actin polymerization and depolymerization, the rate of protein synthesis at the cell body, and the action of cytoskeletal motors (Baas and Ahmad, 2001;Goldberg, 2003;Lamoureux et al, 1989;Mitchison and Kirschner, 1988;O'Toole et al, 2008;Suter and Miller, 2011). Several models of axonal elongation have focused on the sequence of processes based on the production of tubulin dimers at the cell body, the active transport of these proteins to the the tip of the growing axon, and microtubule extension at the growth cone (Graham et al, 2006;Kiddie et al, 2005;McLean and Graham, 2004;Miller and Samulels, 1997;van Veen and van Pelt, 1994).…”

Gradual stretching of the proximal nerve stump induces the growth of regenerating sprouts in rats

“…Furthermore, a linear relationship existed between the growth rate and the experimentally applied tension, and the axonal growth was regulated by mechanical tension. [1][2][3][4][5] Interestingly, the result of our present study suggested that it is also possible to lengthen the regenerating sprouts of the transected proximal nerve stump by the mechanical stretching. Thus, the stimulus of mechanical stretching also induces the growth of regenerating sprouts in vivo.…”

“…In addition, it has been reported that tension applied to the growth cones of PC12 or chick DRG neurites can induces a significant neurite outgrowth. [1][2][3][4][5] In our previous studies, we lengthened the transected proximal nerve stumps by direct gradual stretching ex vivo, and the whole nerve trunk including the endoneurium and axons were lengthened simultaneously in proportion to the stretching period. Interestingly, however, in our experiment the tip of the proximal nerve stump was significantly lengthened during gradual stretching.…”