Stéphane Vincent

Role of Mesodermal FGF8 and FGF10 Overlaps in the Development of the Arterial Pole of the Heart and Pharyngeal Arch Arteries

Rationale: The genes encoding fibroblast growth factor (FGF) 8 and 10 are expressed in the anterior part of the second heart field that constitutes a population of cardiac progenitor cells contributing to the arterial pole of the heart. Previous studies of hypomorphic and conditional Fgf8 mutants show disrupted outflow tract (OFT) and right ventricle (RV) development, whereas Fgf10 mutants do not have detectable OFT defects. Objectives: Our aim was to investigate functional overlap between Fgf8 and Fgf10 during formation of the arterial pole. Methods and Results: We generated mesodermal Fgf8; Fgf10 compound mutants with MesP1Cre. The OFT/RV morphology in these mutants was affected with variable penetrance; however, the incidence of embryos with severely affected OFT/RV morphology was significantly increased in response to decreasing Fgf8 and Fgf10 gene dosage. Fgf8 expression in the pharyngeal arch ectoderm is important for development of the pharyngeal arch arteries and their derivatives. We now show that Fgf8 deletion in the mesoderm alone leads to pharyngeal arch artery phenotypes and that these vascular phenotypes are exacerbated by loss of Fgf10 function in the mesodermal core of the arches. Conclusions: These results show functional overlap of FGF8 and FGF10 signaling from second heart field mesoderm during development of the OFT/RV, and from pharyngeal arch mesoderm during pharyngeal arch artery formation, highlighting the sensitivity of these key aspects of cardiovascular development to FGF dosage.

Macroscopic analysis of gas-jet wiping: Numerical simulation and experimental approach

Coating techniques are frequently used in industrial processes such as paper manufacturing, wire sleeving, and in the iron and steel industry. Depending on the application considered, the thickness of the resulting substrate is controlled by mechanical (scraper), electromagnetic (if the entrained fluid is appropriated), or hydrodynamic (gas-jet wiping) operations. This paper deals with the latter process, referred to as gas-jet wiping, in which a turbulent slot jet is used to wipe the coating film dragged by a moving substrate. This mechanism relies on the gas-jet–liquid film interaction taking place on the moving surface. The aim of this study is to compare the results obtained by a lubrication one–dimensional model, numerical volume of fluid–large eddy simulation (VOF-LES) modeling and an experimental approach. The investigation emphasizes the effect of the controlling wiping parameters, i.e., the pressure gradient and shear stress distributions induced by the jet, on the shape of the liquid film. Those...

Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb

Significance During embryonic development, multipotent stem cells progressively acquire specific cell fates. The somite is an embryological structure that gives rise to different mesodermal cell types, including skeletal muscle and vascular cells of blood vessels. We show by genetic manipulation that the Notch signaling pathway promotes a vascular cell-fate choice at the expense of skeletal muscle in the mouse somite. Pax3+ cells in the adjacent somites give rise to myogenic and endothelial cells in the limbs. Gain-of-function or inhibition of Notch signaling affects this cell-fate choice prior to the migration of these somite-derived cells into the limb. This embryological role of Notch is of potential therapeutic relevance to deriving stem cells for tissue repair. Multipotent Pax3-positive (Pax3+) cells in the somites give rise to skeletal muscle and to cells of the vasculature. We had previously proposed that this cell-fate choice depends on the equilibrium between Pax3 and Foxc2 expression. In this study, we report that the Notch pathway promotes vascular versus skeletal muscle cell fates. Overactivating the Notch pathway specifically in Pax3+ progenitors, via a conditional Pax3NICD allele, results in an increase of the number of smooth muscle and endothelial cells contributing to the aorta. At limb level, Pax3+ cells in the somite give rise to skeletal muscles and to a subpopulation of endothelial cells in blood vessels of the limb. We now demonstrate that in addition to the inhibitory role of Notch signaling on skeletal muscle cell differentiation, the Notch pathway affects the Pax3:Foxc2 balance and promotes the endothelial versus myogenic cell fate, before migration to the limb, in multipotent Pax3+ cells in the somite of the mouse embryo.

The actin cable is dispensable in directing dorsal closure dynamics but neutralizes mechanical stress to prevent scarring in the Drosophila embryo

The actin cable is a supracellular structure that embryonic epithelia produce to close gaps. However, the action of the cable remains debated. Here, we address the function of the cable using Drosophila dorsal closure, a paradigm to understand wound healing. First, we show that the actin cytoskeleton protein Zasp52 is specifically required for actin cable formation. Next, we used Zasp52 loss of function to dissect the mechanism of action of the cable. Surprisingly, closure dynamics are perfect in Zasp52 mutants: the cable is therefore dispensable for closure, even in the absence of the amnioserosa. Conversely, we observed that the cable protects cellular geometries from robust morphogenetic forces that otherwise interfere with closure: the absence of cable results in defects in epithelial organization that lead to morphogenetic scarring. We propose that the cable prevents morphogenetic scarring by stabilizing cellular interactions rather than by acting on closure dynamics.

N,N-Dibenzyl Formamidine as a New Protective Group for Primary Amines

Abstract Primary amines can be converted in high yield into N,N-dibenzyl formamidines under mild conditions. The N,N-dibenzyl formamidine group was found to be effective as a protective group for primary amines as it is stable to a variety of conditions and can be removed by catalytic hydrogenation.

A DPP-mediated feed-forward loop canalizes morphogenesis during Drosophila dorsal closure

During Drosophila dorsal closure, DPP and JNK signaling form a feed-forward loop that controls the specification and differentiation of leading edge cells to ensure robust morphogenesis.

Synthesis of a functionalized GDP-analogue designed for anti-GDP antibody production

Abstract An enzymatically stable analogue of GDP is prepared in 7 steps starting from guanosine. The guanine moiety is functionalized at the N 1 position so as to allow anchoring of the nucleotide onto a carrier protein for subsequent immunization of animals in order to raise antibodies against GDP.

N, N-Dibenzyl Formamide Dimethyl Acetal and N, N-Dibenzyl Chloromethylene Iminium Chloride: Two Complementary Reagents for the Protection Of Primary Amines as N, N-Dibenzyl Formamidines

Abstract Two complementary procedures are described for the preparation of N, N-dibenzyl formamidines from primary amines in high yield. The primary amine protective group can be easily introduced on polyhydroxylated molecules and is removable either by hydrolysis or hydrogenolysis.

A Two-Phase LES Compressible Model for Plasma-Liquid Jet Interaction

The numerical simulation of the interaction between a plasma flow and a liquid jet is important for understanding and predicting the physical parameters involved in plasma spraying processes. This work proposes an original model for dealing with three-dimensional and unsteady turbulent interactions between a plasma flow and a liquid water jet. A compressible model, based on augmented Lagrangian, Large Eddy Simulation (LES) turbulence modeling and Volume of Fluid (VOF) approaches, capable of managing incompressible two-phase flows as well as turbulent compressible motions is presented.