Fig 5. Cellular and tissue deformations during neural tube formation are recapitulated using the 3D vertex model.
Recently, in a collaborative effort with Prof. Naoto Ueno (National Institute for Basic Biology, Okazaki), Prof. Inoue and his team have demonstrated that three physical events at the cellular level are sufficient to mechanically drive neural tube formation - the anlage of the central nervous system that gives rise to the brain and spinal cord - in Xenopus
: apical constriction, cell elongation and cell migration.
* During neural tube closure, cells in the superficial layer of the neuroectoderm undergo apical constriction: actomyosin contractility causes shrinkage of the apical surface area of each cell and leads to a change in cell morphology from a columnar to a wedge-like shape.
* Cells undergoing apical constriction also undergo elongation, whereby cell length (height) increases in the apical-basal direction.
* Prof. Ueno and his team have recently demonstrated that migration of non-neuroectodermal cells in the deep layer (which itself does not give rise to the neural tube) does play a role during neural tube closure.
The 3D vertex model constructed by Prof. Inoue, accounts for the mechanical properties of tissue components and successfully recapitulates tissue deformations during neural tube formation. Using this model, apical constriction, cell elongation, and cell migration were independently perturbed in silico
and their effects on tissue morphology were examined: neural plates of various shapes could thus be observed. Moreover, by experimentally inhibiting apical constriction and cell elongation at the appropriate developmental stage in Xenopus
embryos, Prof. Ueno and his team could show that the resulting cell and tissue shapes resembled the corresponding simulation results, thereby validating the 3D vertex model in vivo
Meanwhile, Prof. Inoue and his team have improved the 3D vertex model by taking into account another physical parameter: the elasticity of the extracellular matrix (ECM). As such, they could convincingly demonstrate that the mechanical properties of the extracellular environment have an impact on neural tube formation and can drastically alter the 3D shape of an epithelial tissue. Indeed, the in silico
simulations of neural tube formation without
cell elongation, showed a causal link between the 3D shape of the neural plate and ECM elasticity. On the other hand, no such relationship could be observed during simulations with
cell elongation (whereby the 3D shape of the neural plate was quasi insensitive to ECM elasticity). These data therefore suggest that robustness - the neural tube adopts its correct 3D shape, despite developmental noise - is ensured by cell elongation during morphogenetic events.