Abstract
The guidance of axons to their proper targets is not only a crucial event in neurodevelopment, but also a potential therapeutic target for neural repair. Axon guidance is mediated by various chemo- and haptotactic cues, as well as the mechanical interactions between the cytoskeleton and the extracellular matrix (ECM). Axonal growth cones, dynamic ends of growing axons, convert external stimuli to biochemical signals, which, in turn, are translated into behavior, e.g., turning or retraction, via cytoskeleton–matrix linkages. Despite the inherent mechanical nature of the problem, the role of mechanics in axon guidance is poorly understood. Recent years has witnessed the application of a range of microtechnologies in neurobiology, from microfluidic circuits to single molecule force spectroscopy. In this mini-review, we describe microtechnologies geared towards dissecting the mechanical aspects of axon guidance, divided into three categories: controlling the growth cone microenvironment, stimulating growth cones with externally applied forces, and measuring forces exerted by the growth cones. A particular emphasis is given to those studies that combine multiple techniques, as dictated by the complexity of the problem.
Highlights
The guidance of axons to their proper targets is a fundamental event in the development of the nervous system, and a potential therapeutic target for repairing the injured nervous system
The important role mechanics plays in axon guidance is more and more widely accepted, a thorough understanding of underlying mechanisms is lacking (Franze et al, 2013). We argue that this is largely due to the low accessibility of the experimental methods that permit mechanical probing of growth cones
We conclude by highlighting recent technologies that are yet to be translated into the axon guidance field
Summary
The guidance of axons to their proper targets is a fundamental event in the development of the nervous system, and a potential therapeutic target for repairing the injured nervous system. The dynamic ends of growing axons, perceive attractive and repulsive cues and translate them into behavior, such as elongation, retraction, or turning (Kalil and Dent, 2005). Despite being tightly regulated by biochemical signals, axonal growth is essentially a series of mechanical processes that eventually drive the growth cone forward or cause its collapse. These processes involve the continuous rearrangement of cytoskeleton, actin filaments (F-actin) and microtubules, in particular (Lowery and Van Vactor, 2009). Force is generated through directed polymerization of cytoskeletal filaments, a process regulated by a range of associated proteins (Dent and Gertler, 2003), or by molecular motors operating on multiple filaments (Geraldo and Gordon-Weeks, 2009)
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