Molecular similarity between the mechanisms of epithelial fusion and fetal wound healing during the closure of the caudal neural tube in mouse embryos

Abstract

Background: Neural tube (NT) closure is a complex developmental process that takes place in the early stages of embryogenesis and that is a key step in neurulation. In mammals, the process by which the neural plate generates the NT requires organized cell movements and tissue folding, and it terminates with the fusion of the apposed ends of the neural folds.Results: Here we describe how almost identical cellular and molecular machinery is used to fuse the spinal neural folds as that involved in the repair of epithelial injury in the same area of the embryo. For both natural and wound activated closure of caudal neural tissue, hyaluronic acid and plateletderived growth factor signaling appear to be crucial for the final fusion step.Conclusions: There seems to be no general wound healing machinery for all tissues but rather, a tissue-specific epithelial fusion machinery that embryos activate when necessary after abnormal epithelial opening.

The loop-tail mouse model displays open and closed caudal neural tube defects

“…Firstly, we thought that the cells may originate from an event similar to wound healing, which, as we have described previously, uses the same molecular machinery as the caudal NT to achieve closure ( Fernández-Santos et al, 2021 ). Thus, we hypothesised that the closure process, owing to morphological abnormalities in the Vangl2 +/Lp neural folds, may be more fragile and needs to be enhanced by the wound healing process.…”

“…S1A-C ). We know from our previous work that during embryonic wound healing in the caudal area of the NT, there is an increased expression of hyaluronic acid (HA), the HA receptor CD44 and platelet-derived growth factor receptor α (PDGFRα, encoded by Pdgfra ; Fernández-Santos et al, 2021 ). Here, as in an induced wound, we observed HA, CD44 and PDGFRα expression in the CA of Vangl2 +/Lp embryos at E11.5-E13.5 ( n =3), suggesting a localised activation of the healing mechanism in the caudal-most closure zone and/or reinforcement from the surface epithelium to complete closure.…”