Somitic mesoderm morphogenesis is necessary for neural tube closure during Xenopus development

Abstract

Neural tube closure is a fundamental process during vertebrate embryogenesis, which leads to the formation of the central nervous system. Defective neural tube closure leads to neural tube defects which are some of the most common human birth defects. While the intrinsic morphogenetic events shaping the neuroepithelium have been studied extensively, how tissues mechanically coupled with the neural plate influence neural tube closure remains poorly understood. Here, using Xenopus laevis embryos, live imaging in combination with loss of function experiments and morphometric analysis of fixed samples we explore the reciprocal mechanical communication between the neural plate and the somitic mesoderm and its impact on tissue morphogenesis. We show that although somitic mesoderm convergent extension occurs independently from neural plate morphogenesis neural tube closure depends on somitic mesoderm morphogenesis. Specifically, impaired somitic mesoderm remodelling results in defective apical constriction within the neuroepithelium and failure of neural tube closure. Last, our data reveal that mild abnormalities in somitic mesoderm and neural plate morphogenesis have a synergistic effect during neurulation, leading to severe neural tube closure defects. Overall, our data reveal that defective morphogenesis of tissues mechanically coupled with the neural plate can not only drastically exacerbate mild neural tube defects that may arise from abnormalities within the neural tissue but can also elicit neural tube defects even when the neural plate is itself free of inherent defects.

Mechanical control of neural plate folding by apical domain alteration

“…Thus, the elongated shape of cells at the hinges may be driven by passive mechanical responses instead of planar polarized junctional shrinking. Notably, while our mosaic RNA and MO injections suggest a role of intrinsic forces in epithelial folding, similar to previous studies 44 , 50 , 51 , they do not exclude the role of global forces derived from the surrounding mesodermal tissues in NT closure. These observations highlight similar roles of mechanical forces in the regulation of cell shape and epithelial tissue dynamics in other systems, especially in Drosophila ventral furrow formation 30 , 52 – 55 .…”

CFL1-dependent dynamicity of surface ectoderm filopodia-like protrusions enhances neurulation zippering speed in mice

“…The lack of spinal phenotypes in embryos lacking CFL1 primarily in the neuroepithelium was unexpected (21). We cannot exclude potential additive or synergistic effects arising from disruptions of different tissues in our Grhl3 Cre model, as previously observed in Xenopus ( 56, 57 ). However, Cdx2 Cre deletes Cfl1 first in the neuroepithelium and then in both the neuroepithelium and surface ectoderm at later stages, but only causes a low penetrance of kinked tail phenotypes consistent with delayed closure.…”

Stepwise modulation of apical orientational cell adhesions for vertebrate neurulation

“…Greater bending at the MHP and DLHPs is facilitated by apical constriction, making these cells adopt a wedged shape. This wedging may be due to intrinsic factors, such as actomyosin‐driven contraction (Christodoulou & Skourides, 2015; Sawyer et al ., 2010), or extrinsic pushing and adhesion forces generated by the expansion of the mesoderm and non‐neural ectoderm and the anchoring of the neural plate to the notochord as well as the pulling force generated by the zippering of the dorsal tips of the neural fold (Christodoulou & Skourides, 2022; de Goederen et al ., 2022). The wedge shape of cells at the MHP and DLHP may suggest stronger parallel OCAs to cohere cells at the apical ends and to support apical constriction than parallel OCAs outside of the hinge points.…”