scholarly journals Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation

2020 ◽  
Author(s):  
Joel Dokmegang ◽  
Moi Hoon Yap ◽  
Liangxiu Han ◽  
Matteo Cavaliere ◽  
René Doursat
Keyword(s):  
Cell Shape ◽  
Computational Modelling ◽  
Tissue Level ◽  
Tissue Mechanics ◽  
Apical Surface ◽  
Biological Cell ◽  
Agent Based ◽  
Cell Shape Changes ◽  
Theoretical Evidence ◽  
Shape Changes

AbstractUnderstanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast and trophectoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a “cup”. Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG#, an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behaviours in silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is sufficient to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed dictates the cup shape of the epiblast and fosters its movement towards the uterine tissue. Together, these results offer mechanical insights into mouse implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.Author summaryComputational modelling is increasingly used in the context of biological development. Here we propose a novel agent-based model of biological cell and tissue mechanics to investigate important morphological changes during mouse embryo implantation. Our model is able to replicate key biological cell shape changes and tissue-level behaviour. Simulating mouse implantation with this model, we bring theoretical support to previous experimental observations that lumenogenesis in the epiblast is driven by repulsion, and provide theoretical evidence that changes in epiblast shape during implantation are regulated by trophectoderm development.

scholarly journals Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254763
Author(s):  
Joel Dokmegang ◽  
Moi Hoon Yap ◽  
Liangxiu Han ◽  
Matteo Cavaliere ◽  
René Doursat
Keyword(s):  
Computational Modelling ◽  
Tissue Level ◽  
Apical Surface ◽  
Mammalian Embryo ◽  
Agent Based ◽  
Mechanical Constraints ◽  
Morphogenetic Event ◽  
Theoretical Evidence ◽  
Experimental Findings ◽  
Modelling Methods

Understanding the processes by which the mammalian embryo implants in the maternal uterus is a long-standing challenge in embryology. New insights into this morphogenetic event could be of great importance in helping, for example, to reduce human infertility. During implantation the blastocyst, composed of epiblast, trophectoderm and primitive endoderm, undergoes significant remodelling from an oval ball to an egg cylinder. A main feature of this transformation is symmetry breaking and reshaping of the epiblast into a “cup”. Based on previous studies, we hypothesise that this event is the result of mechanical constraints originating from the trophectoderm, which is also significantly transformed during this process. In order to investigate this hypothesis we propose MG# (MechanoGenetic Sharp), an original computational model of biomechanics able to reproduce key cell shape changes and tissue level behaviours in silico. With this model, we simulate epiblast and trophectoderm morphogenesis during implantation. First, our results uphold experimental findings that repulsion at the apical surface of the epiblast is essential to drive lumenogenesis. Then, we provide new theoretical evidence that trophectoderm morphogenesis indeed can dictate the cup shape of the epiblast and fosters its movement towards the uterine tissue. Our results offer novel mechanical insights into mouse peri-implantation and highlight the usefulness of agent-based modelling methods in the study of embryogenesis.

scholarly journals Hyperactivation of the folded gastrulation pathway induces specific cell shape changes

Development ◽  
1998 ◽  
Vol 125 (4) ◽  
pp. 589-597 ◽  
Author(s):  
P. Morize ◽  
A.E. Christiansen ◽  
M. Costa ◽  
S. Parks ◽  
E. Wieschaus
Keyword(s):  
Cell Shape ◽  
Inducible Promoter ◽  
Specific Cell ◽  
Apical Surface ◽  
Apical Constriction ◽  
Cellular Effects ◽  
Ventral Furrow ◽  
Cell Shape Changes ◽  
Shape Changes

During Drosophila gastrulation, mesodermal precursors are brought into the interior of the embryo by formation of the ventral furrow. The first steps of ventral furrow formation involve a flattening of the apical surface of the presumptive mesodermal cells and a constriction of their apical diameters. In embryos mutant for folded gastrulation (fog), these cell shape changes occur but the timing and synchrony of the constrictions are abnormal. A similar phenotype is seen in a maternal effect mutant, concertina (cta). fog encodes a putative secreted protein whereas cta encodes an (alpha)-subunit of a heterotrimeric G protein. We have proposed that localized expression of the fog signaling protein induces apical constriction by interacting with a receptor whose downstream cellular effects are mediated by the cta G(alpha)protein. <P> In order to test this model, we have ectopically expressed fog at the blastoderm stage using an inducible promoter. In addition, we have examined the constitutive activation of cta protein by blocking GTP hydrolysis using both in vitro synthesized mutant alleles and cholera toxin treatment. Activation of the fog/cta pathway by any of these procedures results in ectopic cell shape changes in the gastrula. Uniform fog expression rescues the gastrulation defects of fog null embryos but not cta mutant embryos, arguing that cta functions downstream of fog expression. The normal location of the ventral furrow in embryos with uniformly expressed fog suggests the existence of a fog-independent pathway determining mesoderm-specific cell behaviors and invagination. Epistasis experiments indicate that this pathway requires snail but not twist expression.

scholarly journals 3D viscoelastic drag forces drive changes to cell shapes during organogenesis in the zebrafish embryo

2021 ◽  
Author(s):  
Paula C. Sanematsu ◽  
Gonca Erdemci-Tandogan ◽  
Himani Patel ◽  
Emma M. Retzlaff ◽  
Jeffrey D. Amack ◽  
...  
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
New Physics ◽  
Tissue Mechanics ◽  
List Type ◽  
Drag Forces ◽  
Velocity Gradients ◽  
Cell Shapes ◽  
Cell Shape Changes ◽  
Shape Changes

AbstractThe left-right organizer in zebrafish embryos, Kupffer’s Vesicle (KV), is a simple organ that undergoes programmed asymmetric cell shape changes that are necessary to establish the left-right axis of the embryo. We use simulations and experiments to investigate whether 3D mechanical drag forces generated by the posteriorly-directed motion of the KV through the tailbud tissue are sufficient to drive such shape changes. We develop a fully 3D vertex-like (Voronoi) model for the tissue architecture, and demonstrate that the tissue can generate drag forces and drive cell shape changes. Furthermore, we find that tailbud tissue presents a shear-thinning, viscoelastic behavior consistent with those observed in published experiments. We then perform live imaging experiments and particle image velocimetry analysis to quantify the precise tissue velocity gradients around KV as a function of developmental time. We observe robust velocity gradients around the KV, indicating that mechanical drag forces must be exerted on the KV by the tailbud tissue. We demonstrate that experimentally observed velocity fields are consistent with the viscoelastic response seen in simulations. This work also suggests that 3D viscoelastic drag forces could be a generic mechanism for cell shape change in other biological processes.Highlightsnew physics-based simulation method allows study of dynamic tissue structures in 3Dmovement of an organ through tissue generates viscoelastic drag forces on the organthese drag forces can generate precisely the cell shape changes seen in experimentPIV analysis of experimental data matches simulations and probes tissue mechanicsGraphical abstract

Real-time imaging of cell-cell adherens junctions reveals that Drosophila mesoderm invagination begins with two phases of apical constriction of cells

2001 ◽  
Vol 114 (3) ◽  
pp. 493-501 ◽  
Author(s):  
H. Oda ◽  
S. Tsukita
Keyword(s):  
Real Time ◽  
Cell Shape ◽  
Adherens Junctions ◽  
Cell Sheet ◽  
Apical Surface ◽  
Apical Constriction ◽  
Real Time Imaging ◽  
Cell Shape Changes ◽  
Shape Changes ◽  
Cell Cell

Invagination of the epithelial cell sheet of the prospective mesoderm in Drosophila gastrulation is a well-studied, relatively simple morphogenetic event that results from dynamic cell shape changes and cell movements. However, these cell behaviors have not been followed at a sufficiently short time resolution. We examined mesoderm invagination in living wild-type embryos by real-time imaging of fluorescently labeled cell-cell adherens junctions, which are located at the apical zones of cell-cell contact. Low-light fluorescence video microscopy directly visualized the onset and progression of invagination. In an initial period of approximately 2 minutes, cells around the ventral midline reduced their apical surface areas slowly in a rather synchronous manner. Next, the central and more lateral cells stochastically accelerated or initiated their apical constriction, giving rise to random arrangements of cells with small and relatively large apices. Thus, we found that mesoderm invagination began with slow synchronous and subsequent fast stochastic phases of cell apex constriction. Furthermore, we showed that the mesoderm invagination of folded gastrulation mutant embryos lacked the normal two constriction phases, and instead began with asynchronous, feeble cell shape changes. Our observations suggested that Folded gastrulation-mediated signaling enabled synchronous activation of the contractile cortex, causing competition among the individual mesodermal cells for apical constriction. Movies available on-line: http://www.biologists.com/JCS/movies/jcs2073.html

scholarly journals Microtubules enter centre stage for morphogenesis

2020 ◽  
Vol 375 (1809) ◽  
pp. 20190557 ◽  
Author(s):  
Katja Röper
Keyword(s):  
Cell Division ◽  
Cell Shape ◽  
Dynamic Networks ◽  
Tissue Level ◽  
Epithelial Morphogenesis ◽  
Direct Role ◽  
Cell Shape Changes ◽  
Epithelial Sheets ◽  
Cytoskeletal System ◽  
Shape Changes

Cell shape changes are key to observable changes at the tissue level during morphogenesis and organ formation. The major driver of cell shape changes in turn is the actin cytoskeleton, both in the form of protrusive linear or branched dynamic networks and in the form of contractile actomyosin. Over the last 20 years, actomyosin has emerged as the major cytoskeletal system that deforms cells in epithelial sheets during morphogenesis. By contrast, the second major cytoskeletal system, microtubules, have so far mostly been assumed to serve ‘house-keeping' functions, such as directed transport or cell division, during morphogenetic events. Here, I will reflect on a subset of studies over the last 10 years that have clearly shown a major direct role for the microtubule cytoskeleton in epithelial morphogenesis, suggesting that our focus will need to be widened to give more attention and credit to this cytoskeletal system in playing an active morphogenetic role. This article is part of a discussion meeting issue ‘Contemporary morphogenesis'.

scholarly journals A genetic screen for temperature-sensitive morphogenesis-defectiveCaenorhabditis elegansmutants

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Molly C Jud ◽  
Josh Lowry ◽  
Thalia Padilla ◽  
Erin Clifford ◽  
Yuqi Yang ◽  
...  
Keyword(s):  
Cell Shape ◽  
The Body ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Fundamental Biological Process ◽  
Embryonic Morphogenesis ◽  
Cell Shape Changes ◽  
Development Temperature ◽  
Multicellular Organisms ◽  
Shape Changes

AbstractMorphogenesis involves coordinated cell migrations and cell shape changes that generate tissues and organs, and organize the body plan. Cell adhesion and the cytoskeleton are important for executing morphogenesis, but their regulation remains poorly understood. As genes required for embryonic morphogenesis may have earlier roles in development, temperature-sensitive embryonic-lethal mutations are useful tools for investigating this process. From a collection of ∼200 such Caenorhabditis elegans mutants, we have identified 17 that have highly penetrant embryonic morphogenesis defects after upshifts from the permissive to the restrictive temperature, just prior to the cell shape changes that mediate elongation of the ovoid embryo into a vermiform larva. Using whole genome sequencing, we identified the causal mutations in seven affected genes. These include three genes that have roles in producing the extracellular matrix, which is known to affect the morphogenesis of epithelial tissues in multicellular organisms: the rib-1 and rib-2 genes encode glycosyltransferases, and the emb-9 gene encodes a collagen subunit. We also used live imaging to characterize epidermal cell shape dynamics in one mutant, or1219ts, and observed cell elongation defects during dorsal intercalation and ventral enclosure that may be responsible for the body elongation defects. These results indicate that our screen has identified factors that influence morphogenesis and provides a platform for advancing our understanding of this fundamental biological process.

Sign in / Sign up

Export Citation Format

Share Document