By using a zebrafish embryo model to guide the chromatographic fractionation of antimitotic secondary metabolites, seven podophyllotoxin-type lignans were isolated from a hydroalcoholic extract obtained from the steam bark of Bursera fagaroides. The compounds were identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5′-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7). The biological effects on mitosis, cell migration, and microtubule cytoskeleton remodeling of lignans 1–7 were further evaluated in zebrafish embryos by whole-mount immunolocalization of the mitotic marker phospho-histone H3 and by a tubulin antibody. We found that lignans 1, 2, 4, and 7 induced mitotic arrest, delayed cell migration, and disrupted the microtubule cytoskeleton in zebrafish embryos. Furthermore, microtubule cytoskeleton destabilization was observed also in PC3 cells, except for 7. Therefore, these results demonstrate that the cytotoxic activity of 1, 2, and 4 is mediated by their microtubule-destabilizing activity. In general, the in vivo and in vitro models here used displayed equivalent mitotic effects, which allows us to conclude that the zebrafish model can be a fast and cheap in vivo model that can be used to identify antimitotic natural products through bioassay-guided fractionation.

Tissue remodelling and organ shaping during morphogenesis are products of mechanical forces generated at the cellular level. These cell-scale forces can be coordinated across the tissue via information provided by biochemical and mechanical cues. Such coordination leads to the generation of complex tissue shape during morphogenesis. In this short review, we elaborate the role of cellular active stresses in vertebrate axis morphogenesis, primarily using examples from postgastrulation development of the zebrafish embryo.

During development and tissue repair, cells reshape and reconfigure to ensure organs take specific shapes. This process is inherently three-dimensional (3D). Yet, in part due to limitations in imaging and data analysis, cell shape analysis within tissues have been studied as a two-dimensional (2D) approximation, e . g ., the Drosophila wing disc. With recent advances in imaging and machine learning, there has been significant progress in our understanding of 3D cell and tissue shape in vivo . However, even after gaining 3D segmentation of cells, it remains challenging to extract cell shape metrics beyond volume and surface area for cells within densely packed tissues. In order to extract 3D shape metrics, we have developed CellMet. This user-friendly tool enables extraction of quantitative shape information from 3D cell and tissue segmentation. It is developed for extracting cell scale information from densely packed tissues, such as cell face properties, cell twist, and cell rearrangements. Our method will improve the analysis of 3D cell shape and the understanding of cell organisation within tissues. Our tool is open source, available at https://github.com/TimSaundersLab/CellMet .

Withdrawal statement: The authors have withdrawn their manuscript owing to significant errors in figures 1, 3, 6, and supplementary figure 3. Also, because some of the results were incorrectly reported. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.