Formation of polarized contractile interfaces by self-organized Toll-8/Cirl GPCR asymmetry

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Evo–Devo: Universal Toll Pass for the Extension Highway?

International audienceThe distinction between long-germ and short-germ insects is a classic one in evo-devo, yet a common genetic mechanism may underlie germband extension in all insects, even all arthropods

Fat2 and Lar Dance a Pas de Deux during Collective Cell Migration

International audienceWhat coordinates the internal leading and trailing edges in collectively migrating cells is largely unknown. In this issue of Developmental Cell, Barlan et al. (2017) delineate a Fat2/Lar planar signaling pathway at the basal, motile cell-cell contacts of Drosophila egg chamber follicle cells

L'initiation et le pré-modèle du bourgeon de la nageoire, pilotés par la convergence cellulaire asymétrique, nécessitent le contrôle par Tbx5a d'un signal Fgf mésenchymateux.

International audienceTbx5 plays a pivotal role in vertebrate forelimb initiation and loss-of-function experiments result in deformed or absent forelimbs in all taxa studied to date. Combining single-cell fate mapping and 3D cell tracking in the zebrafish, we describe a Tbx5a-dependent cell convergence pattern that is both asymmetric and topological within the fin-field lateral plate mesoderm during early fin bud initiation. We further demonstrate that a mesodermal Fgf24 convergence cue controlled by Tbx5a underlies this asymmetric convergent motility. Partial reduction in Tbx5a or Fgf24 levels disrupts the normal fin-field cell motility gradient and results in anteriorly biased perturbations of fin-field cell convergence and truncations in the pectoral fin skeleton, resembling aspects of the forelimb skeletal defects that define Holt-Oram Syndrome patients. This study provides a quantitative reference model for fin-field cell motility during vertebrate fin bud initiation and suggests that a pre-pattern of AP fate specification is already present in the fin-field before or during migration as perturbations to these early cell movements result in the alteration of specific fates.Tbx5 joue un rôle central dans l'initiation des membres antérieurs des vertébrés et les expériences de perte de fonction se traduisent par des membres antérieurs déformés ou absents chez tous les taxons étudiés à ce jour. En combinant la cartographie du destin d'une cellule unique et le suivi cellulaire en 3D chez le poisson zèbre, nous décrivons un modèle de convergence cellulaire dépendant de Tbx5a qui est à la fois asymétrique et topologique dans le mésoderme de la plaque latérale du champ des nageoires pendant l'initiation précoce du bourgeon de nageoire. Nous démontrons également qu'un indice de convergence mésodermique Fgf24 contrôlé par Tbx5a sous-tend cette motilité convergente asymétrique. Une réduction partielle des niveaux de Tbx5a ou de Fgf24 perturbe le gradient normal de motilité des cellules du champ de nageoires et entraîne des perturbations de la convergence des cellules du champ de nageoires et des tronçons du squelette de la nageoire pectorale, ressemblant à certains aspects des défauts du squelette des membres antérieurs qui définissent les patients atteints du syndrome de Holt-Oram. Cette étude fournit un modèle de référence quantitatif pour la motilité des cellules du champ de nageoires pendant l'initiation du bourgeon de nageoire des vertébrés et suggère qu'un pré-modèle de spécification du destin des PA est déjà présent dans le champ de nageoires avant ou pendant la migration, car les perturbations de ces mouvements cellulaires précoces entraînent l'altération de destins spécifiques

The effect of Astragalus polysaccharides on attenuation of diabetic cardiomyopathy through inhibiting the extrinsic and intrinsic apoptotic pathways in high glucose -stimulated H9C2 cells

Abstract Background Apoptosis plays a critical role in the progression of diabetic cardiomyopathy (DC). Astragalus polysaccharides (APS), an extract of astragalus membranaceus (AM), is an effective cardioprotectant. Currently, little is known about the detailed mechanisms underlying cardioprotective effects of APS. The aims of this study were to investigate the potential effects and mechanisms of APS on apoptosis employing a model of high glucose induction of apoptosis in H9C2 cells. Methods A model of high glucose induction of H9C2 cell apoptosis was adopted in this research. The cell viabilities were analyzed by MTT assay, and the apoptotic response was quantified by flow cytometry. The expression levels of the apoptosis related proteins were determined by Real-time PCR and western blotting. Results Incubation of H9C2 cells with various concentrations of glucose (i.e., 5.5, 12.5, 25, 33 and 44 mmol/L) for 24 h revealed that cell viability was reduced by high glucose dose-dependently. Pretreatment of cells with APS could inhibit high glucose-induced H9C2 cell apoptosis by decreasing the expressions of caspases and the release of cytochrome C from mitochondria to cytoplasm. Further experiments also showed that APS could modulate the ratio of Bcl-2 to Bax in mitochondria. Conclusions APS decreases high glucose-induced H9C2 cell apoptosis by inhibiting the expression of pro-apoptotic proteins of both the extrinsic and intrinsic pathways and modulating the ratio of Bcl-2 to Bax in mitochondria

The evolution of courtship behaviours through the origination of a new gene in Drosophila

New genes can originate by the combination of sequences from unrelated genes or their duplicates to form a chimeric structure. These chimeric genes often evolve rapidly, suggesting that they undergo adaptive evolution and may therefore be involved in novel phenotypes. Their functions, however, are rarely known. Here, we describe the phenotypic effects of a chimeric gene, sphinx, that has recently evolved in Drosophila melanogaster. We show that a knockout of this gene leads to increased male¿male courtship in D. melanogaster, although it leaves other aspects of mating behavior unchanged. Comparative studies of courtship behavior in other closely related Drosophila species suggest that this mutant phenotype of male¿male courtship is the ancestral condition because these related species show much higher levels of male¿male courtship than D. melanogaster. D. melanogaster therefore seems to have evolved in its courtship behaviors by the recruitment of a new chimeric gene

Tension-driven multi-scale self-organisation in human iPSC-derived muscle fibers

Human muscle is a hierarchically organised tissue with its contractile cells called myofibers packed into large myofiber bundles. Each myofiber contains periodic myofibrils built by hundreds of contractile sarcomeres that generate large mechanical forces. To better understand the mechanisms that coordinate human muscle morphogenesis from tissue to molecular scales, we adopted a simple in vitro system using induced pluripotent stem cell-derived human myogenic precursors. When grown on an unrestricted two-dimensional substrate, developing myofibers spontaneously align and self-organise into higher-order myofiber bundles, which grow and consolidate to stable sizes. Following a transcriptional boost of sarcomeric components, myofibrils assemble into chains of periodic sarcomeres that emerge across the entire myofiber. More efficient myofiber bundling accelerates the speed of sarcomerogenesis suggesting that tension generated by bundling promotes sarcomerogenesis. We tested this hypothesis by directly probing tension and found that tension build-up precedes sarcomere assembly and increases within each assembling myofibril. Furthermore, we found that myofiber ends stably attach to other myofibers using integrin-based attachments and thus myofiber bundling coincides with stable myofiber bundle attachment in vitro. A failure in stable myofiber attachment results in a collapse of the myofibrils. Overall, our results strongly suggest that mechanical tension across sarcomeric components as well as between differentiating myofibers is key to coordinate the multi-scale self-organisation of muscle morphogenesis

Tension-driven multi-scale self-organisation in human iPSC-derived muscle fibers

Human muscle is a hierarchically organised tissue with its contractile cells called myofibers packed into large myofiber bundles. Each myofiber contains periodic myofibrils built by hundreds of contractile sarcomeres that generate large mechanical forces. To better understand the mechanisms that coordinate human muscle morphogenesis from tissue to molecular scales, we adopted a simple in vitro system using induced pluripotent stem cell-derived human myogenic precursors. When grown on an unrestricted two-dimensional substrate, developing myofibers spontaneously align and self-organise into higher-order myofiber bundles, which grow and consolidate to stable sizes. Following a transcriptional boost of sarcomeric components, myofibrils assemble into chains of periodic sarcomeres that emerge across the entire myofiber. More efficient myofiber bundling accelerates the speed of sarcomerogenesis suggesting that tension generated by bundling promotes sarcomerogenesis. We tested this hypothesis by directly probing tension and found that tension build-up precedes sarcomere assembly and increases within each assembling myofibril. Furthermore, we found that myofiber ends stably attach to other myofibers using integrin-based attachments and thus myofiber bundling coincides with stable myofiber bundle attachment in vitro. A failure in stable myofiber attachment results in a collapse of the myofibrils. Overall, our results strongly suggest that mechanical tension across sarcomeric components as well as between differentiating myofibers is key to coordinate the multi-scale self-organisation of muscle morphogenesis