Journal
BIOMECHANICS AND MODELING IN MECHANOBIOLOGY
Volume 15, Issue 6, Pages 1733-1746Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s10237-016-0794-1
Keywords
Neural tube closure; 3D vertex simulation; Apical constriction; Cell elongation; Cell migration
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Funding
- MEXT/JSPS KAKENHI [15H05861 15KT0154 15H05865]
- Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Dynamic Approaches to Living System) from the Japan Agency for Medical Research and Development (AMED)
- Grants-in-Aid for Scientific Research [15H04380, 15KT0154, 15K07088, 15H05856, 15H05865, 15H05861] Funding Source: KAKEN
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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.
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