Mechanics of neurulation: From classical to current perspectives on the physical mechanics that shape, fold, and form the neural tube

Abstract

Neural tube defects arise from mechanical failures in the process of neurulation. At the most fundamental level, formation of the neural tube relies on coordinated, complex tissue movements that mechanically transform the flat neural epithelium into a lumenized epithelial tube (Davidson, 2012). The nature of this mechanical transformation has mystified embryologists, geneticists, and clinicians for more than 100 years. Early embryologists pondered the physical mechanisms that guide this transformation. Detailed observations of cell and tissue movements as well as experimental embryological manipulations allowed researchers to generate and test elementary hypotheses of the intrinsic and extrinsic forces acting on the neural tissue. Current research has turned toward understanding the molecular mechanisms underlying neurulation. Genetic and molecular perturbation have identified a multitude of subcellular components that correlate with cell behaviors and tissue movements during neural tube formation. In this review, we focus on methods and conceptual frameworks that have been applied to the study of amphibian neurulation that can be used to determine how molecular and physical mechanisms are integrated and responsible for neurulation. We will describe how qualitative descriptions and quantitative measurements of strain, force generation, and tissue material properties as well as simulations can be used to understand how embryos use morphogenetic programs to drive neurulation. Birth Defects Research 109:153-168, 2017. © 2016 Wiley Periodicals, Inc.

Keywords: biomechanics; biophysics; cell mechanics; epithelia; epithelial folding; morphogenesis; neural tube defects; quantitative analysis.

Figure 1:. Concurrent mechanical processes shape the neural tube in Xenopus laevis.

A) Stage-dependency of specific tissue deforming processes (black bars) and cell behaviors (purple bars) that accompany the different phases of neurulation in Xenopus laevis. We refer interested readers to a similar diagram describing tissue movements and cell behaviors during stages of chick neurulation (Schoenwolf and Smith, 1990). B) Transverse sections and maximally z-projected en face sections of F-actin stained cell outlines of the posterior neural and non-neural dorsal ectoderm in fixed Xenopus laevis embryos showing cell and tissue morphological changes at each stage of neurulation.

Figure 2:. Formal definitions of mechanical terminology.

Engineering provides specific terms to create mechanical descriptions of biological processes. Provided are commonly used definitions that demonstrate the relationship between strain, stress and material properties.

Figure 3:. Simulating the mechanics of neurulation with physical analogs and computational models.

A) Physical analog model of fold formation in an elastic sheet. Tensile force is applied (yellow arrow) causing lateral buckling and fold formation. B) Physical analog model of laser ablation. Cells boundaries represented by network of elastic rubber bands under differential tension and with differential elasticity. When a single rubber band is cut, tension is released and network recoils. The instantaneous velocity of recoil reflects both the tension and mechanical properties of cell sheets in laser ablation experiments. C) Computational vertex-model of cell rearrangement during neural plate shaping in the chick. Patterns of cell-cell adhesion are predicted to produce aligned rows through directed cell rearrangement (modified from Fig. 2 in Nishimura et al., 2012; with authors' permission). D) Continuum model of axolotl neurulation. Finite element model based on image-acquired 3D geometry (modified from Figure 9 in Chen and Brodland, 2008; with authors' permission).