Biology subjects

Tlili, S. L.

Publications and source records attributed to Tlili, S. L..

4 recordsLinked to original sources

bioRxiv2024

Inferring the location and orientation of cell divisions on time-lapse image sequences

We propose a two-stage supervised framework for characterizing cell divisions in 2D and 3D time-lapse microscopy. First, we recast division detection as a semantic segmentation task on image sequences. Second, a local regression model estimates the orientation and distance between daughter cells for each event. We validate this framework using image sequences of avian neuroepithelium and mouse gastruloids. Our results demonstrate that high performance is achieved with efficient architectures, namely a U-Net for segmentation and a CNN for regression, that are optimized through systematic hyperparameter exploration. We find that integrating temporal context via multiple consecutive frames significantly boosts segmentation accuracy. We achieve F1 scores exceeding 94% (2D+t) and 90% (3D+t), with orientation accuracy approaching the uncertainty limit of manual annotation. We provide the full codebase and training workflow, specifically designed for datasets where traditional tracking is challenging.

biophysics↗

bioRxiv2023

Marangoni-like tissue flows enhance symmetry breaking of embryonic organoids

During early development of multi-cellular animals, cells self-organize to set up the body axes, such as the primary head-to-tail axis, based on which the later body plan is defined. Several signaling pathways are known to control body axis formation. Here, we show, however, that also tissue mechanics plays an important role during this process. We focus on the emergence of a primary axis in initially spherical aggregates of mouse embryonic stem cells, which mirrors events in the early mouse embryo. These aggregates break rotational symmetry to establish an axial organization with domains of different expression profiles, e.g. of the transcription factor T/Bra and the adhesion molecule E-cadherin. Combining quantitative microscopy and physical modeling, we identify large-scale tissue flows with a recirculation component and demonstrate that they significantly contribute to symmetry breaking. We show that the recirculating flows are explained by a difference in tissue surface tension across domains, akin to Marangoni flows, which we further confirm by aggregate fusion experiments. Our work highlights that body axis formation is not only driven by biochemical processes, but that it can also be amplified by tissue flows. We expect that this type of amplification may operate in many other organoid and in-vivo systems.

biophysics↗

bioRxiv2023

The positioning mechanics of microtubule asters in Drosophila embryo explants

Microtubule asters are essential in localizing the action of microtubules in processes including mitosis and organelle positioning. In large cells, such as the one-cell sea urchin embryo, aster dynamics are dominated by hydrodynamic pulling forces. However, in systems with more densely positioned nuclei such as the early Drosophila embryo, which packs around 6000 nuclei within the syncytium in a crystalline-like order, it is unclear what processes dominate aster dynamics. Here, we take advantage of a cell cycle regulation Drosophila mutant to generate embryos with multiple asters, independent from nuclei. We use an ex vivo assay to further simplify this biological system to explore the forces generated by and between asters. Through live imaging, drug and optical perturbations, and theoretical modelling, we demonstrate that these asters likely generate an effective pushing force over short distances. Significance StatementUsing cytosolic explants from Drosophila syncytial embryos combined with quantitative microscopy and perturbations, de-Carvalho et al., reveal the mechanical forces separating Drosophila microtubule asters. Aster separation drives precise nuclear positioning in multinucleated embryo cells, a vital process for tissue formation and gene expression during subsequent embryo development.

biophysics↗

bioRxiv2022

A microfluidic platform to investigate the role of mechanical constraints on tissue reorganization

Mechanical constraints have a high impact on development processes, and there is a need for new tools to investigate the role of mechanosensitive pathways in tissue reorganization during development. We present here experiments where embryonic cell aggregates are aspired through constrictions in microfluidic channels, generating highly heterogeneous flows and high cell deformations that can be imaged using two-photon microscopy. This approach provides a way to measure in situ local viscoelastic properties of 3D tissues and connect them to intracellular and intercellular events such as cell shape changes and cell rearrangements. Perspectives include applications on organoids to investigate and quantify rheological properties of tissues, and to understand how constraints affect development.

biophysics↗