Mechanical tension can specify axonal fate in hippocampal neurons

Abstract

Here we asked whether applied mechanical tension would stimulate undifferentiated minor processes of cultured hippocampal neurons to become axons and whether tension could induce a second axon in an already polarized neuron. Experimental tension applied to minor processes produced extensions that demonstrated axonal character, regardless of the presence of an existing axon. Towed neurites showed a high rate of spontaneous growth cone advance and could continue to grow out for 1–3 d after towing. The developmental course of experimental neurites was found to be similar to that of unmanipulated spontaneous axons. Furthermore, the experimentally elongated neurites showed compartmentation of the axonal markers dephospho-tau and L-1 in towed outgrowth after 24 h. Extension of a second axon from an already polarized neuron does not lead to the loss of the spontaneous axon either immediately or after longer term growth. In addition, we were able to initiate neurites de novo that subsequently acquired axonal character even though spontaneous growth cone advance began while the towed neurite was still no longer than its sibling processes. This suggests that tension rather than the achievement of a critical neurite length determined axonal specification.

A Molecular Clutch between the Actin Flow and N-Cadherin Adhesions Drives Growth Cone Migration

“…1 D), indicating that the neuritogenic effect of N-cadherin is driven by a stimulation of growth cone migration. The linear relationship agrees with the concept that growth cones extend neurites by pulling on them, the velocity of growth cones being translated into a constant rate of neurite extension (Lamoureux et al, 2002). Those effects were specific of N-cadherin adhesion because addition of the calcium chelator EGTA or the GC4 antibody to block N-cadherin homophilic binding drastically reduced growth cone advance and neurite extension (Fig.…”

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

“…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. 45 SiNWs were deflected by cells cultured on SiNW substrates by being first pulled into the center of cell. The deflected SiNWs have restoration force, which pulls the cells into the center of the SiNW.…”

Nanoscale Surface Topography Reshapes Neuronal Growth in Culture

“…On the contrary, chemical cues like laminin produces a specific signal at the molecular level, which allows it to induce a modulated response depending on its concentration 20 The mechanisms at the origin of the accelerated neurite elongation provided by the fragmentation of adhesive surfaces are still unknown, and only speculative hypothesis could be formulated at this stage. Among them, an increase of neurite tension, resulting from the spacing between adhesion points could be pertinent for two reasons: stretching neurites results in an accelerated elongation that eventually lead to their differentiation into axons 28 , and axons displayed periodic actin rings wrapped around their circumference spaced by a submicrometric distances 29 . These actin rings may have a role in sustaining the mechanical strains to which axons are subjected.…”