Neural tube closure: cellular, molecular and biomechanical mechanisms

Abstract

Neural tube closure has been studied for many decades, across a range of vertebrates, as a paradigm of embryonic morphogenesis. Neurulation is of particular interest in view of the severe congenital malformations -'neural tube defects' -that result when closure fails. The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2. More recently, biomechanical inputs into neural tube morphogenesis have also been identified. Here, we review these cellular, molecular and biomechanical mechanisms involved in neural tube closure, based on studies of various vertebrate species, focusing on the most recent advances in the field.

Wnt regulates amino acid transporter Slc7a5 and so constrains the integrated stress response in mouse embryos

“…Fibroblast growth factor (Fgf) 8 locally regulates expansion of key embryonic tissues, including in the developing brain and limb [28,29] and is co-expressed in the rostral forebrain with FoxG1/BF1 [30]. As Fgf8 and FoxG1 are correctly localised, these data suggest that Slc7a5 loss does not disrupt overall tissue patterning, but attenuates expansion of cell populations in the developing brain and limb, which can compromise morphogenetic cell movements, such as those underlying neural tube closure [31]. As Fgf8 and FoxG1 are correctly localised, these data suggest that Slc7a5 loss does not disrupt overall tissue patterning, but attenuates expansion of cell populations in the developing brain and limb, which can compromise morphogenetic cell movements, such as those underlying neural tube closure [31].…”

Contributions of the chick embryo and experimental embryology to understanding the cellular mechanisms of neurulation

“…Thus, in contrast to the first premise of the classical model for neural plate bending, cell wedging is not occurring throughout the neuroepithelium but is instead restricted to localized regions called hinge points. Similar hinge points and localized areas of cell wedging also form in the mouse neural plate (McShane et al, 2015;Nikolopoulou et al, 2017).…”

“…Thus, cell nuclei occupy multiple apicobasal positions within the epithelium, and as they progress through the cell cycle, they undergo interkinetic nuclear migration, that is, nuclei move apically as they replicate their DNA, undergo cytokinesis at the apex of the epithelium, and their daughter cell nuclei migrate basally as they immediately reenter the cell cycle, with a negligible G0/G1 period. Similarly, in the mouse neural plate, cell nuclei occupy multiple apicobasal positions within the epithelium and interkinetic nuclear migration occurs (Nikolopoulou et al, 2017).…”

“…Recent studies, based largely on mouse mutants, have revealed that convergent extension during shaping of the neural plate is regulated through the planar cell polarity (PCP) pathway (reviewed by Nikolopoulou et al, 2017; also see Ciruna et al, 2006;Curtin et al, 2003;Wallingford and Harland, 2002), consistent with both cell intercalation being the motor for convergent extension in the neural plate and the process being an organ-autonomous event.…”

Configuring a robust nervous system with Fat cadherins

“…The developing neural tube closes at three independent sites [71]. Closure at site 1 depends on well-characterized PCP events that ensure convergent extension and hence elongation of the caudal neural tube.…”