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Biology subjects

Leggio, B.

Publications and source records attributed to Leggio, B..

4 recordsLinked to original sources

An Interpretable Framework to Characterize Compound Treatments on Filamentous Fungi using Cell Painting and Deep Metric Learning

The cell painting microscopy imaging protocol has recently gained traction in the biology community as it allows, through the addition of fluorescent dyes, to acquire images that highlight intra-cellular components that are not visible through traditional whole-cell microscopy. While previous works have successfully applied cell painting to mammalian cells, we devise a staining protocol applicable to a filamentous fungus model. Following a principled visual inspection and annotation protocol of phenotypes by domain-experts, we devise an efficient, robust, and conceptually simple image analysis strategy based on the Deep Cosine Metric Learning paradigm that allows to estimate phenotypical similarities across different imaging modalities. We experimentally demonstrate the benefits of our pipeline in the tasks of estimating dose-response curves over a wide range of subtle phenotypical variations. Last, we showcase how our learned metrics can group image samples according to different modes of action and biological targets in an interpretable manner.

bioinformatics↗

A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control

The link between gene regulation and morphogenesis of multicellular organisms is a fundamental problem in biology. We address this question in the floral meristem of Arabidopsis, which generates new tissues and organs through complex changes in growth patterns. Starting from high-resolution time-lapse images, we generated a comprehensive 4-D atlas of early flower development including cell lineage, cellular growth rates and the expression patterns of 28 regulatory genes. This information was introduced in MorphoNet, a web-based open-access platform. The application of mechanistic computational models indicated that the molecular network based on the literature only explained a minority of the expression patterns. This was substantially improved by adding single regulatory hypotheses for individual genes. We next used the integrated information to correlate growth with the combinatorial expression of multiple genes. This led us to propose a set of hypotheses for the action of individual genes in morphogenesis, not visible by simply correlating gene expression and growth. This identified the central transcription factor LEAFY as a potential regulator of heterogeneous growth, which was supported by quantifying growth patterns in a leafy mutant. By providing an integrated, multiscale view of flower development, this atlas should represent a fundamental step towards mechanistic multiscale-scale models of flower development.

developmental biology↗

Multiscale mechanical model for cell division orientation in developing biological systems

Developing biological structures are highly complex systems, within which shape dynamics at different places is tightly coordinated. One key process at play during development is the regulation of cell division orientation. In this work, through a reformulation of cell division in terms of its energetic cost, we propose that oriented cell division is one mechanism by which cells can read and react to mechanical forces propagating in a tissue even in the absence of interphase cellular elongation in the direction of these forces. This view reproduces standard geometric division long-axis rules as a special case of a more general behaviour, in which systematic deviations from these rules can emerge. We show that states of anisotropic tension in multicellular systems can be the cause of these deviations, as often experimentally found in living tissues. Our results provide a unifying view on the different intracellular mechanisms at play in orienting cell division: they are processes which minimize energy loss, reflecting a trade-off between local and long-range mechanical signals. The consequences of this competition are explored in simulated tissues and confirmed in vivo during both the development of the pupal epithelium of dorsal thorax in D. melanogaster and the epidermal morphogenesis of ascidian embryos. Author summaryIn this work we reformulate the process of cell division orientation in development as a mechanical-energy optimization. We show that classical rules for division orientation naturally emerge when a cell minimizes the work performed against its local environment. Moreover, when multicellular stress profiles are taken into account, observed systematic violations of these rules are explained in correlation with states of anisotropic tension within the tissue. We confirm our findings experimentally on developing systems imaged with cellular resolution. Our results provide a new paradigm to understand cell division in multicellular contexts and contribute to building a physical view of biological phenomena.

biophysics↗

Contact-dependent cell communications drive morphological invariance during ascidian embryogenesis

Canalization of developmental processes ensures the reproducibility and robustness of embryogenesis within each species. In its extreme form, found in ascidians, early embryonic cell lineages are invariant between embryos within and between species, despite rapid genomic divergence. To resolve this paradox, we used live light-sheet imaging to quantify individual cell behaviors in digitalized embryos and explore the forces that canalize their development. This quantitative approach revealed that individual cell geometries and cell contacts are strongly constrained, and that these constraints are tightly linked to the control of fate specification by local cell inductions. While in vertebrates ligand concentration usually controls cell inductions, we found that this role is fulfilled in ascidians by the area of contacts between signaling and responding cells. We propose that the duality between geometric and genetic control of inductions contributes to the counterintuitive inverse correlation between geometric and genetic variability during embryogenesis.

developmental biology↗