Sequential Contraction and Exchange of Apical Junctions Drives Zippering and Neural Tube Closure in a Simple Chordate

Abstract

Unidirectional zippering is a key step in neural tube closure that remains poorly understood. Here, we combine experimental and computational approaches to identify the mechanism for zippering in a basal chordate, Ciona intestinalis. We show that myosin II is activated sequentially from posterior to anterior along the neural/epidermal (Ne/Epi) boundary just ahead of the advancing zipper. This promotes rapid shortening of Ne/Epi junctions, driving the zipper forward and drawing the neural folds together. Cell contact rearrangements (Ne/Epi + Ne/Epi → Ne/Ne + Epi/Epi) just behind the zipper lower tissue resistance to zipper progression by allowing transiently stretched cells to detach and relax toward isodiametric shapes. Computer simulations show that measured differences in junction tension, timing of primary contractions, and delay before cell detachment are sufficient to explain the speed and direction of zipper progression and highlight key advantages of a sequential contraction mechanism for robust efficient zippering.

Biomechanical coupling facilitates spinal neural tube closure in mouse embryos

“…Inference of cellular biomechanics by laser ablation in simpler organisms is well-established (11,(39)(40)(41)(42), but is substantially complicated in mouse embryos by their comparatively large size, complex shape, and tissue opacity. Here we investigated the effects of needle and laser ablations on tissue morphology many cell diameters away from the ablation site in live-imaged embryos.…”

“…Studies in experimentally tractable ascidians and lower vertebrates have mapped mechanical stresses that are normally withstood within and around the neuroepithelium. This work has identified cellular behaviors, such as actomyosin-driven apical constriction of neural plate cells, required to initiate apposition of the neural folds (11)(12)(13)(14)(15)(16). Genetic or pharmacologic disruption of actin remodeling enzymes prevents NT closure in amphibians as well as in mice (16)(17)(18)(19).…”

Nodal and FGF coordinate ascidian neural tube morphogenesis

“…Eventually, the lateral plate borders, aided by force from the surrounding epidermis (Ogura et al, 2011), meet at the dorsal midline together with the adjacent epidermis. Sequential contractions and rearrangements of neural-epidermal junctions cause a progressive posterior-to-anterior fusion of the epidermis overlying the neural tube following involution (Hashimoto et al, 2015).…”

Switching the rate and pattern of cell division for neural tube closure

“…The central nervous system of urochordate ascidian consists of fewer than 400 neural cells, and the cell lineages of neural cells and neighboring surface ectodermal cells have been well described 4,35,36 . These characteristics are advantageous for the analysis of neural cell behaviors, and thus the cellular mechanism of neural fold fusion was recently revealed in the ascidian Ciona intestinalis 37 . Actomyosin-driven rearrangement of the apical cell junction is a well-established mechanism of cell shape change that can promote morphogenesis (Fig.…”

“…2B). 37 These apical junction rearrangement events between NE and SE occur repeatedly, thereby zipping-up the neural plate into a tube. Although this mechanism is primarily important for the directional progression of the zippering in Ciona , filopodia is also observed, which may support the progression of the process of zippering 33 …”