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Cavaliere, M.

Publications and source records attributed to Cavaliere, M..

3 recordsLinked to original sources

Quantification of cell behaviours and computational modelling show that cell directional behaviours drive zebrafish pectoral fin morphogenesis

MotivationUnderstanding the mechanisms by which the zebrafish pectoral fin develops is expected to produce insights on how vertebrate limbs grow from a 2D cell layer to a 3D structure. Two mechanisms have been proposed to drive limb morphogenesis in tetrapods: a growth-based morphogenesis with a higher proliferation rate at the distal tip of the limb bud than at the proximal side, and directed cell behaviors that include elongation, division and migration in a nonrandom manner. Based on quantitative experimental biological data at the level of individual cells in the whole developing organ, we test the conditions for the dynamics of pectoral fin early morphogenesis. ResultsWe found that during the development of the zebrafish pectoral fin, cells have a preferential elongation axis that gradually aligns along the proximodistal axis (PD) of the organ. Based on these quantitative observations, we build a center-based cell model enhanced with a polarity term and cell proliferation to simulate fin growth. Our simulations resulted in 3D fins similar in shape to the observed ones, suggesting that the existence of a preferential axis of cell polarization is essential to drive fin morphogenesis in zebrafish, as observed in the development of limbs in the mouse, but distal tip-based expansion is not. AvailabilityUpon publication, biological data will be available at http://bioemergences.eu/modelingFin, and code source at https://github.com/guijoe/MaSoFin. Contactjoel.dokmegang-kassap@stu.mmu.ac.uk, nadine.peyrieras@cnrs.fr or rene.doursat@iscpif.fr Supplementary informationSupplementary data are included in this manuscript.

systems biology↗

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

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 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 summary Computational 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.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗

Organoid And Tissue Patterning Through Phase Separation: Use Of A Vertex Model To Relate Dynamics Of Patterning To Underlying Biophysical Parameters

AO_SCPLOWBSTRACTC_SCPLOWExactly a century ago, DArcy Thompson set an agenda for understanding tissue development in terms of underlying biophysical, mathematically-tractable mechanisms. One such mechanism, discovered by Steinberg in the 1960s, is adhesion-mediated sorting of cell mixtures into homotypic groups. Interest in this phase separation mechanism has recently surged, partly because of its use to create synthetic biological patterning mechanisms and partly because it has been found to drive events critical to the formation of organoids from stem cells, making the process relevant to biotechnology as well as to basic development. Here, we construct quantitative model of patterning by phase separation, informed by laboratory data, and use it to explore the relationship between degree of adhesive difference and speed, type and extent of resultant patterning. Our results can be used three ways; to predict the outcome of mix-ing cells with known properties, to estimate the properties required to make some designed organoid system, or to estimate underlying cellular properties from observed behaviour.

developmental biology↗