scholarly journals Seven Challenges in the Multiscale Modelling of Multicellular Tissues

2020 ◽  
Author(s):  
Alexander Fletcher ◽  
James Osborne
Keyword(s):  
Cell Shape ◽  
Recent Progress ◽  
Ex Vivo ◽  
Computational Modelling ◽  
Multiscale Modelling ◽  
Comprehensive Understanding ◽  
Spatial And Temporal Scales ◽  
Growth Mechanics ◽  
Shape Changes ◽  
Coupling Cell

The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviours, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regeneration is to understand how relationships between scales produce emergent tissue-scale behaviours. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionised our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modelling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics and signalling. Yet such models remain technically challenging: modelling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarise recent progress in multiscale modelling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation and validation of such models.

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 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.

scholarly journals Bone Mass Distribution of the Distal Tibia in Normal, Osteopenic, and Osteoporotic Conditions: An Ex Vivo Assessment Using HR-pQCT, DXA, and Computational Modelling

2016 ◽  
Vol 99 (6) ◽  
pp. 588-597 ◽  
Author(s):  
Lukas Kamer ◽  
Hansrudi Noser ◽  
Michael Blauth ◽  
Mark Lenz ◽  
Markus Windolf ◽  
...  
Keyword(s):  
Bone Mass ◽  
Mass Distribution ◽  
Ex Vivo ◽  
Distal Tibia ◽  
Computational Modelling

Estradiol promotes cell shape changes and glial fibrillary acidic protein redistribution in hypothalamic astrocytes in vitro: A neuronal-mediated effect

Glia ◽  
1992 ◽  
Vol 6 (3) ◽  
pp. 180-187 ◽  
Author(s):  
Ignacio Torres-Aleman ◽  
Maria Teresa Rejas ◽  
Sebastian Pons ◽  
Luis Miguel Garcia-Segura
Keyword(s):  
Glial Fibrillary Acidic Protein ◽  
Cell Shape ◽  
Acidic Protein ◽  
Cell Shape Changes ◽  
Shape Changes

scholarly journals The first “Slit” is the deepest: the secret to a hollow heart

2008 ◽  
Vol 182 (2) ◽  
pp. 221-223 ◽  
Author(s):  
Iiro Taneli Helenius ◽  
Greg J. Beitel
Keyword(s):  
Cell Shape ◽  
Vascular System ◽  
Hollow Heart ◽  
Autocrine Signaling ◽  
Lumen Formation ◽  
Membrane Surfaces ◽  
Vascular Morphogenesis ◽  
Cell Biol ◽  
Shape Changes

Tubular organs are essential for life, but lumen formation in nonepithelial tissues such as the vascular system or heart is poorly understood. Two studies in this issue (Medioni, C., M. Astier, M. Zmojdzian, K. Jagla, and M. Sémériva. 2008. J. Cell Biol. 182:249–261; Santiago-Martínez, E., N.H. Soplop, R. Patel, and S.G. Kramer. 2008. J. Cell Biol. 182:241–248) reveal unexpected roles for the Slit–Robo signaling system during Drosophila melanogaster heart morphogenesis. In cardioblasts, Slit and Robo modulate the cell shape changes and domains of E-cadherin–based adhesion that drive lumen formation. Furthermore, in contrast to the well-known paracrine role of Slit and Robo in guiding cell migrations, here Slit and Robo may act by autocrine signaling. In addition, the two groups demonstrate that heart lumen formation is even more distinct from typical epithelial tubulogenesis mechanisms because the heart lumen is bounded by membrane surfaces that have basal rather than apical attributes. As the D. melanogaster cardioblasts are thought to have significant evolutionary similarity to vertebrate endothelial and cardiac lineages, these findings are likely to provide insights into mechanisms of vertebrate heart and vascular morphogenesis.

Autonomy and non-autonomy in Drosophila mesoderm determination and morphogenesis

Development ◽  
1994 ◽  
Vol 120 (4) ◽  
pp. 853-859 ◽  
Author(s):  
M. Leptin ◽  
S. Roth
Keyword(s):  
Cell Shape ◽  
Shape Change ◽  
Developmental Program ◽  
Cell Shape Change ◽  
Ventral Furrow ◽  
Large Numbers ◽  
The Individual ◽  
Mutant Cells ◽  
Transplantation Experiments ◽  
Shape Changes

The mesoderm in Drosophila invaginates by a series of characteristic cell shape changes. Mosaics of wild-type cells in an environment of mutant cells incapable of making mesodermal invaginations show that this morphogenetic behaviour does not require interactions between large numbers of cells but that small patches of cells can invaginate independent of their neighbours' behaviour. While the initiation of cell shape change is locally autonomous, the shapes the cells assume are partly determined by the individual cell's environment. Cytoplasmic transplantation experiments show that areas of cells expressing mesodermal genes ectopically at any position in the egg form an invagination. We propose that ventral furrow formation is the consequence of all prospective mesodermal cells independently following their developmental program. Gene expression at the border of the mesoderm is induced by the apposition of mesodermal and non-mesodermal cells.

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