Tension-driven axon assembly: a possible mechanism

Citation: Heidemann SR and Bray D (2015) Tension-driven axon assembly: a possible mechanism. As the contents of this issue of " Frontiers " attest, the study of the mechanical aspects of neuronal development has come a long way since the 1970's and 80's when we became interested in the topic. The vast majority of cells in multicellular organisms are continually pushed and pulled, compressed, and stretched throughout their life and a diversity of mechanisms have evolved to protect against and harness these forces. Nerve cells are no exception, and several excellent reviews in recent years have examined ways in which mechanical inputs influence their development and function However, it seems to us that certain aspects of this response have not been given the attention they deserve. In particular tension-driven axon assembly seems to be in a class of its own and quite distinct from other effects of tension such as modifications of cell migration, perturbation of division cycles, or changes in synthetic activity. Axon growth under these conditions is an exaggerated transformation of a nerve cell manifest by the prolonged accretion of new cellular material. Under the right circumstances, the rate and extent of this mass addition is remarkably large, to the degree that it implies an unusual, possibly unique mechanism. A pulled axon grows as though the nerve cell contained telescopic machinery prefabricated for elongation. But the identity of this nascent structure (if it exists), where it is stored, and how it is triggered to self-assemble into axon, remain to be discovered. Mature axons have been known to be under tension since the early days of neuroanatomy. Harrison described the second phase of growth in which axons, having reached their target tissue while the axon is very short, increase their length coordinate with surrounding tissues—referring to it as " passive stretching " (Harrison, 1935). Weiss (1941) explicitly postulated that growth following synaptogenesis was due to mechanical tension. He described the " towing " of the axon as a result of the migration of the post-synaptic cell, as in the lateral line organ of zebrafish (Gilmour et al., 2004). Much later it became evident that mechanical tension has an essential role in the other, first phase of growth. Growth cones from individual sympathetic neurons growing in culture were recorded migrating away from the cell soma, pulling out neurites as they went (Bray, 1979). Vectorial analysis of the outgrowths produced in …