The emerging role of forces in axonal elongation

Suter, Daniel M.; Miller, Kyle E.

doi:10.1016/j.pneurobio.2011.04.002

Cited by 198 publications

(222 citation statements)

References 148 publications

(217 reference statements)

Supporting

Mentioning

213

Contrasting

Unclassified

Order By: Relevance

“…a pulling force; see Glossary, Box 1) (Bray, 1979;Heidemann and Buxbaum, 1994;Pfister et al, 2004;Siechen et al, 2009;Suter and Miller, 2011). This tension may be quantified with calibrated microneedles: forces are applied to neurites, and the change in neurite length and the deflection of the needle (which is proportional to the applied force) are measured (Dennerll et al, 1988).…”

Section: Cellular Forces and Tensionmentioning

confidence: 99%

“…Furthermore, interactions between actin filaments and microtubules, which modify stress distributions in the growth cone, are required for growth cone motility and turning (Geraldo and Gordon-Weeks, 2009). Growth cone traction forces finally oppose the tension that is acting along neurites (Bray, 1979; Dennerll et al, 1988;Heidemann and Buxbaum, 1994; Ayali, 2010;Suter and Miller, 2011) (see below). While the mechanisms of force application are comparatively well understood, how mechanical input is translated into an intracellular, biochemical response ('mechanotransduction') is currently ill defined.…”

mentioning

confidence: 99%

“…2) (Dennerll et al, 1989). For excellent recent reviews about neuronal tension see Ayali (Ayali, 2010) and Suter and Miller (Suter and Miller, 2011). Such tensile forces are generated and maintained by the growth cone (Lamoureux et al, 1989;Lamoureux et al, 2010), by the interaction of actin and myosin along the neurite (Dennerll et al, 1988), and by target cells pulling on the neurite (Weiss, 1941), and they are potentially involved in many different aspects of the development of the nervous system.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The mechanical control of nervous system development

2013

View full text Add to dashboard Cite

The development of the nervous system has so far, to a large extent, been considered in the context of biochemistry, molecular biology and genetics. However, there is growing evidence that many biological systems also integrate mechanical information when making decisions during differentiation, growth, proliferation, migration and general function. Based on recent findings, I hypothesize that several steps during nervous system development, including neural progenitor cell differentiation, neuronal migration, axon extension and the folding of the brain, rely on or are even driven by mechanical cues and forces.Key words: Mechanics, Mechanosensitivity, Mechanotaxis, Mechanotransduction, Stiffness, Force, Tension, Brain folding Introduction Many processes in development involve growth and motion on different length and time scales. All of these processes are driven by forces; the development of organisms and organ systems would not proceed without mechanics. For example, during neuronal development, neurons migrate and extend immature processes (neurites), which become axons and dendrites. Axons then grow in two different phases, both of which are distinguished by the nature of the forces that drive the growth. In the first phase, growth cones at the tips of axonal processes actively exert forces on their environment (Betz et al., 2011), thus pulling on the processes (Lamoureux et al., 1989). In a second phase, after connecting with their target tissue, axons may be passively pulled by the increasing distance between target and nervous tissue, resulting in considerable growth in length, a process referred to as stretch growth (Weiss, 1941). Once the final connectivity is established, tension may develop along neuronal axons, which may be involved in neuronal network formation and the folding of the brain. Apart from this direct requirement of forces for developmental processes, which has been studied to some degree in the past, the mechanical interaction of cells with their environment may add an additional level of control to several processes in the developing nervous system, including progenitor cell differentiation and cellular guidance.The idea of an important contribution of mechanics to the development of the nervous system has been around for more than a century. However, recent decades have seen only little progress in this field compared with other (e.g. electrophysiology, molecular biology or genetics-based) areas of neuroscience. Progress often depends on the availability of appropriate methodology. Only recently has the increasing involvement of physical and engineering approaches in interdisciplinary studies of biological systems led to the development of new techniques and conceptual approaches that can be used to quantitatively probe and control relevant mechanical parameters, such as cell and tissue stiffness, cellular forces, and tension. In recent years, such tissue mechanics-based studies have resulted in an increasing awareness of the importance of physical parameters, particularly in developm...

show abstract

Section: Cellular Forces and Tensionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

The mechanical control of nervous system development

2013

View full text Add to dashboard Cite

show abstract

“…This has been demonstrated for different classes of transmembrane receptors (Giannone et al, 2009;Moore et al, 2009;Moore et al, 2010). Such linkage of F-actin to the extracellular environment generates mechanical forces across the membrane, which can trigger intracellular signalling events (referred to as the 'clutch' mechanism) that then can influence actin and MT dynamics (Suter and Forscher, 2000;Suter and Miller, 2011). display minimal redundancy in the fly genome. For example, eliminating the function of Ena/VASP requires a triple knockout in mouse, whereas only a single gene needs to be removed in Drosophila Kwiatkowski et al, 2007).…”

Section: Box 1 Abps and Mtbps As Essential Regulators Of Cytoskeletamentioning

confidence: 99%

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

Prokop

Beaven

et al. 2013

Journal of Cell Science

View full text Add to dashboard Cite

SummaryThe extension of long slender axons is a key process of neuronal circuit formation, both during brain development and regeneration. For this, growth cones at the tips of axons are guided towards their correct target cells by signals. Growth cone behaviour downstream of these signals is implemented by their actin and microtubule cytoskeleton. In the first part of this Commentary, we discuss the fundamental roles of the cytoskeleton during axon growth. We present the various classes of actin-and microtubule-binding proteins that regulate the cytoskeleton, and highlight the important gaps in our understanding of how these proteins functionally integrate into the complex machinery that implements growth cone behaviour. Deciphering such machinery requires multidisciplinary approaches, including genetics and the use of simple model organisms. In the second part of this Commentary, we discuss how the application of combinatorial genetics in the versatile genetic model organism Drosophila melanogaster has started to contribute to the understanding of actin and microtubule regulation during axon growth. Using the example of dystonin-linked neuron degeneration, we explain how knowledge acquired by studying axonal growth in flies can also deliver new understanding in other aspects of neuron biology, such as axon maintenance in higher animals and humans.

show abstract

“…The outgrowth of axons to their targets and the formation and stabilization of synaptic contacts are critically dependent on adhesion of the neuron to extracellular substrates during outgrowth and subsequently to target cells (Raper and Mason, 2010;Benson and Huntley, 2012). These sites of adhesion provide the linkages to transduce forces generated by the cytoskeleton that drive axonal outgrowth and shape, developing synaptic specializations (Suter and Miller, 2011). However, neurons do not grow in isolation, but rather in the context of the growth of the entire organism.…”

Section: Introductionmentioning

confidence: 99%

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

et al. 2014

View full text Add to dashboard Cite

We describe the identification of zyxin as a regulator of synapse maintenance in mechanosensory neurons in C. elegans. zyx-1 mutants lacked PLM mechanosensory synapses as adult animals. However, most PLM synapses initially formed during development but were subsequently lost as the animals developed. Vertebrate zyxin regulates cytoskeletal responses to mechanical stress in culture. Our work provides in vivo evidence in support of such a role for zyxin. In particular, zyx-1 mutant synaptogenesis phenotypes were suppressed by disrupting locomotion of the mutant animals, suggesting that zyx-1 protects mechanosensory synapses from locomotion-induced forces. In cultured cells, zyxin is recruited to focal adhesions and stress fibers via C-terminal LIM domains and modulates cytoskeletal organization via the N-terminal domain. The synapse-stabilizing activity was mediated by a short isoform of ZYX-1 containing only the LIM domains. Consistent with this notion, PLM synaptogenesis was independent of α-actinin and ENA-VASP, both of which bind to the N-terminal domain of zyxin. Our results demonstrate that the LIM domain moiety of zyxin functions autonomously to mediate responses to mechanical stress and provide in vivo evidence for a role of zyxin in neuronal development.

show abstract

The emerging role of forces in axonal elongation

Cited by 198 publications

References 148 publications

The mechanical control of nervous system development

The mechanical control of nervous system development

Using fly genetics to dissect the cytoskeletal machinery of neurons during axonal growth and maintenance

The conserved LIM domain-containing focal adhesion protein ZYX-1 regulates synapse maintenance inCaenorhabditis elegans

Contact Info

Product

Resources

About