The mechanical control of nervous system development

Abstract

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...

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