Browsing by Author "Sharpe, James"
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Publication 4D reconstruction of murine developmental trajectories using spherical harmonics.(Cell Press, 2022-09-12) Dalmasso, Giovanni; Musy, Marco; Niksic, Martina; Robert-Moreno, Alexandre; Badia-Careaga, Claudio; Sanz-Ezquerro, Juan Jose; Sharpe, James; European Molecular Biology Laboratory; Unión Europea. Comisión Europea. European Research Council (ERC); Fundación La Marató TV3Normal organogenesis cannot be recapitulated in vitro for mammalian organs, unlike in species including Drosophila and zebrafish. Available 3D data in the form of ex vivo images only provide discrete snapshots of the development of an organ morphology. Here, we propose a computer-based approach to recreate its continuous evolution in time and space from a set of 3D volumetric images. Our method is based on the remapping of shape data into the space of the coefficients of a spherical harmonics expansion where a smooth interpolation over time is simpler. We tested our approach on mouse limb buds and embryonic hearts. A key advantage of this method is that the resulting 4D trajectory can take advantage of all the available data while also being able to interpolate well through time intervals for which there are little or no data. This allows for a quantitative, data-driven 4D description of mouse limb morphogenesis.Publication Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme.(The Company of Biologists, 2007-10) Arques, Carlos G; Doohan, Roisin; Sharpe, James; Torres, Miguel; Ministerio de Educación y Ciencia (España); International Human Frontier Science Program Organization; Unión Europea. Comisión Europea; Ministerio de Sanidad y Consumo (España); Fundación ProCNICRegionalization of embryonic fields into independent units of growth and patterning is a widespread strategy during metazoan development. Compartments represent a particular instance of this regionalization, in which unit coherence is maintained by cell lineage restriction between adjacent regions. Lineage compartments have been described during insect and vertebrate development. Two common characteristics of the compartments described so far are their occurrence in epithelial structures and the presence of signaling regions at compartment borders. Whereas Drosophila compartmental organization represents a background subdivision of embryonic fields that is not necessarily related to anatomical structures, vertebrate compartment borders described thus far coincide with, or anticipate, anatomical or cell-type discontinuities. Here, we describe a general method for clonal analysis in the mouse and use it to determine the topology of clone distribution along the three limb axes. We identify a lineage restriction boundary at the limb mesenchyme dorsoventral border that is unrelated to any anatomical discontinuity, and whose lineage restriction border is not obviously associated with any signaling center. This restriction is the first example in vertebrates of a mechanism of primordium subdivision unrelated to anatomical boundaries. Furthermore, this is the first lineage compartment described within a mesenchymal structure in any organism, suggesting that lineage restrictions are fundamental not only for epithelial structures, but also for mesenchymal field patterning. No lineage compartmentalization was found along the proximodistal or anteroposterior axes, indicating that patterning along these axes does not involve restriction of cell dispersion at specific axial positions.Publication Quantification of gene expression patterns to reveal the origins of abnormal morphogenesis(eLife Sciences Publications, 2018-09-20) Martinez-Abadias, Neus; Mateu Estivill, Roger; Sastre Tomas, Jaume; Perrine, Susan Motch; Yoon, Melissa; Robert-Moreno, Alexandre; Swoger, Jim; Russo, Lucia; Kawasaki, Kazuhiko; Richtsmeier, Joan; Sharpe, JamesThe earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which are hard to detect and can be obscured later in development by secondary effects. Here, we develop a method to trace back the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying Geometric Morphometrics to 3D gene expression data obtained by Optical Projection Tomography, we determined that our approach is sensitive enough to find regulatory abnormalities that have never been detected previously. We identified subtle but significant differences in the gene expression of a downstream target of a Fgfr2 mutation associated with Apert syndrome, demonstrating that these mouse models can further our understanding of limb defects in the human condition. Our method can be applied to different organ systems and models to investigate the etiology of malformations.