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Guevorkian, K.

Publications and source records attributed to Guevorkian, K..

4 recordsLinked to original sources

Activity-driven extracellular volume expansion drives vertebrate axis elongation

The vertebrate bauplan is primarily established via the formation of embryonic tissues in a head-to-tail progression. The biomechanics of this elongation, which requires the presomitic mesoderm (PSM), remains poorly understood. Here, we find that avian PSM explants can elongate autonomously when physically confined in vitro, producing a pushing force that can largely account for the posterior elongation of the embryo. Tissue elongation results from volumetric expansion that is driven by cellular activity and accompanied by inhomogeneous increase of the extracellular fraction along the AP axis. We show that FGF signaling promotes glycolysis-dependent production of Hyaluronic Acid (HA), which is required for expansion of the posterior PSM. Our findings link body axis elongation to tissue expansion through the metabolic control of extracellular matrix production downstream of FGF signaling. One-Sentence SummaryActive tissue expansion propels body elongation independent of cell proliferation-driven growth

developmental biology↗

Actin modulates shape and mechanics of tubular membranes

The actin cytoskeleton shapes cells and also organizes internal membranous compartments. In particular, it interacts with membranes in intracellular transport of material in mammalian cells, yeast or plant cells. Tubular membrane intermediates, pulled along microtubule tracks, are involved during these processes, and destabilize into vesicles. While the role of actin in this destabilization process is still debated, literature also provide examples of membranous structures stabilization by actin. To directly address this apparent contradiction, we mimic the geometry of tubular intermediates with preformed membrane tubes. The growth of an actin sleeve at the tube surface is monitored spatio-temporally. Depending on network cohesiveness, actin is able to stabilize, or maintain membrane tubes under pulling. Indeed, on a single tube, thicker portions correlate with the presence of actin. Such structures relax over several minutes, and may provide enough time and curvature geometries for other proteins to act on tube stability.

biophysics↗

Motility-gradient induced elongation of the vertebrate embryo

The body of vertebrate embryos forms by posterior elongation from a terminal growth zone called the Tail Bud (TB). The TB produces highly motile cells forming the presomitic mesoderm (PSM), a tissue playing an important role in elongation movements. PSM cells establish an anterior-posterior cell motility gradient which parallels the degradation of a specific cellular signal (Fgf8) known to be implicated in cell motility. Here, we combine electroporation of fluorescent reporters in the PSM to time-lapse imaging in the chicken embryo to quantify cell diffusive movements along the motility gradient. We show that simple microscopic and macroscopic mechano-chemical models for tissue extension that couple Fgf activity, cell motility and tissue rheology at both the cellular and continuum levels suffice to capture the speed and extent of elongation. These observations explain how the continuous addition of cells that exhibit a gradual reduction in motility combined with lateral confinement can be converted into an oriented movement that drives body elongation. The results of the models compare well with our experimental results, with implications for other elongation processes in the embryo.

developmental biology↗

Warburg-like metabolism coordinates FGF and Wnt signaling in the vertebrate embryo

Mammalian embryos transiently exhibit aerobic glycolysis (Warburg effect), a metabolic adaptation also observed in cancer cells. The role of this particular type of metabolism during vertebrate organogenesis is currently unknown. Here, we provide evidence for spatio-temporal regulation of aerobic glycolysis in the posterior region of mouse and chicken embryos. We show that a posterior glycolytic gradient is established in response to graded transcription of glycolytic enzymes downstream of FGF signaling. We demonstrate that glycolysis controls posterior elongation of the embryonic axis by regulating cell motility in the presomitic mesoderm and by controlling specification of the paraxial mesoderm fate in the tail bud. Our results suggest that Warburg metabolism in the tail bud coordinates Wnt and FGF signaling to promote elongation of the embryonic axis.

developmental biology↗