Mechanical roles of apical constriction, cell elongation, and cell migration during neural tube formation in Xenopus

Abstract

Neural tube closure is an important and necessary process during the development of the central nervous system. The formation of the neural tube structure from a flat sheet of neural epithelium requires several cell morphogenetic events and tissue dynamics to account for the mechanics of tissue deformation. Cell elongation changes cuboidal cells into columnar cells, and apical constriction then causes them to adopt apically narrow, wedge-like shapes. In addition, the neural plate in Xenopus is stratified, and the non-neural cells in the deep layer (deep cells) pull the overlying superficial cells, eventually bringing the two layers of cells to the midline. Thus, neural tube closure appears to be a complex event in which these three physical events are considered to play key mechanical roles. To test whether these three physical events are mechanically sufficient to drive neural tube formation, we employed a three-dimensional vertex model and used it to simulate the process of neural tube closure. The results suggest that apical constriction cued the bending of the neural plate by pursing the circumference of the apical surface of the neural cells. Neural cell elongation in concert with apical constriction further narrowed the apical surface of the cells and drove the rapid folding of the neural plate, but was insufficient for complete neural tube closure. Migration of the deep cells provided the additional tissue deformation necessary for closure. To validate the model, apical constriction and cell elongation were inhibited in Xenopus laevis embryos. The resulting cell and tissue shapes resembled the corresponding simulation results.Electronic supplementary materialThe online version of this article (doi:10.1007/s10237-016-0794-1) contains supplementary material, which is available to authorized users.

Biomechanical coupling facilitates spinal neural tube closure in mouse embryos

“…The apical surface area of NMP zone cells decreased relative to their initial size during 1 h of live imaging (Fig. 4B), documenting in mammalian embryos a process that is known to biomechanically mediate neural fold midline approximation in lower vertebrates (14,19,33). The surface area of surface ectoderm cells immediately rostral to the zippering point did not change significantly over the same time period (SI Appendix, section 1, Fig.…”

“…Here we show that the zippering point also serves a biomechanical function, with its physical ablation resulting in rapid lateral displacement of the neural folds and consequent PNP widening. Biomechanically active components involved in NT formation have been studied primarily in Xenopus, in which apical constriction has been implicated in bending of the bilayered neuroepithelium (14,19,44). Actomyosin contraction is an evolutionarily conserved force-generating mechanism, with resulting forces transmitted between biomechanically coupled cells primarily through cadherin/catenin adherens junctions (45,46).…”

“…Studies in experimentally tractable ascidians and lower vertebrates have mapped mechanical stresses that are normally withstood within and around the neuroepithelium. This work has identified cellular behaviors, such as actomyosin-driven apical constriction of neural plate cells, required to initiate apposition of the neural folds (11)(12)(13)(14)(15)(16). Genetic or pharmacologic disruption of actin remodeling enzymes prevents NT closure in amphibians as well as in mice (16)(17)(18)(19).…”

Frequency and synchrony of actomyosin oscillation during PCP-dependent convergent extension

“…Mathematical modeling has become a powerful tool for exploring complex biological events, including collective cell movements during morphogenesis (Szabó et al, 2016, Inoue et al, 2016, Alt et al, 2017, Yu and Fernandez-Gonzalez, 2017. Collective cell movements emerge in vivo from the coordination of actomyosin contractile systems both within cells and between cells (Guillot and Lecuit, 2013, Heisenberg and Bellaiche, 2013, Mao and Baum, 2015.…”

Model to link cell shape and polarity with organogenesis

“…Theoretical 33 models have been important for understanding tubulogenesis, however they are often 34 limited to 2D and thus focus on either wedging or CE [15][16][17]. While there are 3D 35 models for budding and neurulation [18,19], they lack the coupling between PCP, 36 wedging and CE and do not capture the entire sheet-to-tube transition. To close this 37 gap we introduce a model of polarized cell-cell interactions where cells are treated as 38 point particles.…”