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Biomedical subjects

Vincent Fleury

Publications and source records attributed to Vincent Fleury.

6 recordsLinked to original sources

Dynamics of vascular branching morphogenesis: the effect of blood and tissue flow.

Vascularization of embryonic organs or tumors starts from a primitive lattice of capillaries. Upon perfusion, this lattice is remodeled into branched arteries and veins. Adaptation to mechanical forces is implied to play a major role in arterial patterning. However, numerical simulations of vessel adaptation to haemodynamics has so far failed to predict any realistic vascular pattern. We present in this article a theoretical modeling of vascular development in the yolk sac based on three features of vascular morphogenesis: the disconnection of side branches from main branches, the reconnection of dangling sprouts ("dead ends"), and the plastic extension of interstitial tissue, which we have observed in vascular morphogenesis. We show that the effect of Poiseuille flow in the vessels can be modeled by aggregation of random walkers. Solid tissue expansion can be modeled by a Poiseuille (parabolic) deformation, hence by deformation under hits of random walkers. Incorporation of these features, which are of a mechanical nature, leads to realistic modeling of vessels, with important biological consequences. The model also predicts the outcome of simple mechanical actions, such as clamping of vessels or deformation of tissue by the presence of obstacles. This study offers an explanation for flow-driven control of vascular branching morphogenesis.

Animals↗

Molecular mechanisms of early lung specification and branching morphogenesis.

The "hard wiring" encoded within the genome that determines the emergence of the laryngotracheal groove and subsequently early lung branching morphogenesis is mediated by finely regulated, interactive growth factor signaling mechanisms that determine the automaticity of branching, interbranch length, stereotypy of branching, left-right asymmetry, and finally gas diffusion surface area. The extracellular matrix is an important regulator as well as a target for growth factor signaling in lung branching morphogenesis and alveolarization. Coordination not only of epithelial but also endothelial branching morphogenesis determines bronchial branching and the eventual alveolar-capillary interface. Improved prospects for lung protection, repair, regeneration, and engineering will depend on more detailed understanding of these processes. Herein, we concisely review the functionally integrated morphogenetic signaling network comprising the critical bone morphogenetic protein, fibroblast growth factor, Sonic hedgehog, transforming growth factor-beta, vascular endothelial growth factor, and Wnt signaling pathways that specify and drive early embryonic lung morphogenesis.

Animals↗

About the equilibrium shape of fibred structures, and biological shapes.

Biological morphogenesis has often been modeled with reaction-diffusion models [A.M. Turing, The chemical basis of morphogenesis, Phil. Trans. R. Soc. Lond. B 237 (1952) 37-72]. The interplay of bio-chemical fields is supposed to generate shapes by positional information carried by the values in the field. However, the structure of the biological tissue at the microscopic scale is absent from these models. We show that the fibred nature of biological tissue induces specific morphogenic properties. Fibred shapes can be calculated from physical principles borrowed from the theory of crystallogenesis. These give an intuitive insight into the shape of fruits or vegetables, buds and pins in botany, fingers, muscles, insects abdomen and heart in the animal realm, and also into other fibred structures such as the mitotic spindle. We predict the existence of bumps, apices or cusps at poles of fibred structures. An extrapolation to out-of-equilibrium growth predicts that these structures grow forward in the direction of the cusp, and that fibred organs should have a regular branching ordering. However, our model does not take into account the elasto-plastic properties, or the composite nature of the living material.

Biophysical Phenomena↗

Flow regulates arterial-venous differentiation in the chick embryo yolk sac.

Formation of the yolk sac vascular system and its connection to the embryonic circulation is crucial for embryo survival in both mammals and birds. Most mice with mutations in genes involved in vascular development die because of a failure to establish this circulatory loop. Surprisingly, formation of yolk sac arteries and veins has not been well described in the recent literature. Using time-lapse video-microscopy, we have studied arterial-venous differentiation in the yolk sac of chick embryos. Immediately after the onset of perfusion, the yolk sac exhibits a posterior arterial and an anterior venous pole, which are connected to each other by cis-cis endothelial interactions. To form the paired and interlaced arterial-venous pattern characteristic of mature yolk sac vessels, small caliber vessels of the arterial domain are selectively disconnected from the growing arterial tree and subsequently reconnected to the venous system, implying that endothelial plasticity is needed to fashion normal growth of veins. Arterial-venous differentiation and patterning are controlled by hemodynamic forces, as shown by flow manipulation and in situ hybridization with arterial markers ephrinB2 and neuropilin 1, which show that expression of both mRNAs is not genetically determined but plastic and regulated by flow. In vivo application of ephrinB2 or EphB4 in the developing yolk sac failed to produce any morphological effects. By contrast, ephrinB2 and EphB4 application in the allantois of older embryos resulted in the rapid formation of arterial-venous shunts. In conclusion, we show that flow shapes the global patterning of the arterial tree and regulates the activation of the arterial markers ephrinB2 and neuropilin 1.

Animals↗

Rapid electroplating of insulators.

Electrochemical techniques for depositing metal films and coatings have a long history. Such techniques essentially fall into two categories, with different advantages and disadvantages. The first, and oldest, makes use of spontaneous redox reactions to deposit a metal from solution, and can be used on both insulating and metallic substrates. But the deposition conditions of these processes are difficult to control in situ, in part because of the variety of salts and additives present in the solution. The second approach-electroplating-uses an electric current to reduce metal ions in solution, and offers control over the quantity (and, to some extent, grain size) of deposited metal. But application of this technique has hitherto been restricted to conducting substrates. Here we describe an electroplating technique that permits coating of insulating substrates with metals having controlled grain size, thickness and growth speed. The basis of our approach is the progressive outward growth of the metal from an electrode in contact with the substrate, with the cell geometry chosen so that the electron current providing the reduction passes through the growing deposit. Such an approach would normally form dendritic or powdery deposits, but we identify a range of conditions in which uniform films rapidly form.

Journal Article↗

Morphogenesis of fingers and branched organs: how collagen and fibroblasts break the symmetry of growing biological tissue.

Understanding the growth of branching organs is an important scientific endeavour. It has crucial applications, from saving premature newborns, to repairing or even regenerating organs. Despite differences in timing and shape, branching morphogenesis of all branching organs or glands (lung, kidney, salivary, lachrymal, mammary glands, sebaceous and sweat glands, prostate, guts papillae etc.) is similar: an epithelial sheet of cells, forming a 2D layer, penetrates into a 3D mass of mesenchymal cells. Inside the epithelium, a lumen is filled with fluid. As the epithelium grows, it evolves into a branched structure. The pattern of branches is in some cases stereotypic, deterministic, and it has memory effects. We present a simple line of reasoning that predicts that viscous fingering of biological tissue will exhibit all of these features. The line of reasoning is based on the idea that surface tension selects the shape of a growing branch, as is well known in the context of moving boundary problems, except that in this case, the surface is akin to a liquid-crystal. The anisotropy of the surface tension comes from a symmetry breaking by collagen and fibroblasts. The equilibrium shape of the corresponding boundary is that of an actual fingertip, and the out-of-equilibrium shape is that of branched organs, such as the lung.

Animals↗