Symmetry breaking andde-novoaxis formation inhydraspheroids: the microtubule cytoskeleton as a pivotal element

Abstract

The establishment of polarity in cells and tissues is one of the first steps in multicellular development. The 'eternal embryo' hydra can completely regenerate from a disorganised cell cluster or a small fragment of tissue of about 10, 000 cells. During regeneration, the cells first form a hollow cell spheroid, which then undergoes de-novo symmetry breaking to irreversibly polarise. Here, we address the symmetry-related shape changes. Prior to axis establishment, the spherical aggregates of regenerating cells show highly coordinated mechanical oscillations on several timescales that are isotropic in space. There are transient periods of fluctuations in defined arbitrary directions, until these undergo a clearly identified irreversible transition to directed fluctuations along the future main axis of the regenerating hydra. Stabilised cytosolic actin structures disappear during the de-novo polarisation, while polymerised microtubules remain. Drugs that depolymerise actin filaments accelerate the symmetry breaking process, while drug-stabilised actin filaments prevent it. Nocodazole-depolymerised microtubules prevent symmetry breaking, but it can be rescued by the microtubule-stabilising drug paclitaxel at concentrations where microtubular structures start to reappear. We discuss the possibility that these mechanical fluctuations induce the orientation of the microtubules, which contribute to β -catenin nuclear translocation, to increase the organiserforming-potential of the cells. Our data suggest that in regenerating hydra spheroids, the biomechanical shape fluctuations are an integral part of the cooperative polarisation of the self-organising hydra, during which microtubules play a pivotal role.

Spatio-temporal Coordination of Active Deformation Forces and Wnt / Hippo-Yap Signaling inHydraRegeneration

“…1b ). This is clearly different from previous studies, where specimens were fixed in agar gels or confined in hanging liquid droplets (18), which affects the whole deformation dynamics of the system. To define the biomechanical symmetry breaking geometrically during Hydra regeneration, we Fourier transformed the radial distance between the contour and the center of mass r ( θ, t ) of the specimens during the whole regeneration process that took about 90 h (Fig.…”

“…1a right) (16, 17) plays a key role in Hydra regeneration. Ott and co-workers monitored the deformation of regenerates embedded in agar gels (16) or in droplets (18), and proposed that the morphological symmetry breaking occurs at the time point when the frequency of periodic deformation becomes higher. Keren and co-workers monitored the orientation of actin fibers in regenerates taken from different body parts, and suggested that the actin fiber orientation inherited from the parent animal determines the body axis after regeneration (19).…”

Evaluation of Acacia- Guar Gum Combination as Delayed Release Coating Former on Solid Placebo Tablets

“…The most fundamental property of gum Arabic its water solubility and high viscosity but does not thicken the product. It has approved by FDA as pharmaceutical products that use in a wide variety of applications mainly as tablet binder, film forming agent, emulsifier, and suspending agent [11]. Gum Arabic is a multifunctional hydrocolloid with a highly branched arabinogalactan protein complex; it is often described as globular in shape.…”