Bio

Bio


I am a postdoctoral scholar in the department of Developmental Biology and Genetics under the supervision of Dr. Maria Barna. I obtained a master degree in developmenatl biology, immunology and neurobiology from the University of Marseille in France during which I worked under the supervion of Dr. Patrick Lemaire working on transcription regulation in ascidia and Dr. Christophe Marcelle working on somite differentiation in the chick. After my master I decided to join the laboratory of Pr. Olivier Pourquie at the Stowers Institute for Medical Research in Kansas City and start to work on the role of Hox proteins in the regulation of the axial elongation of vertebrate embryos. Our lab moved to the IGBMC in Strasbourg France where I finished my PhD.

Honors & Awards


  • Master fellowship, the French Ministry of Education and Science (2006-2008)
  • PhD fellowship, the French Ministry of Education and Science (2008-2011)
  • graduate student travel award, Society for Developmental Biology (2011)

Professional Education


  • License, Universite D'Aix-Marseille Ii (2005)
  • Master of Science, Universite D'Aix-Marseille Ii (2007)
  • Doctorat, Universite De Strasbourg (2011)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


I am interested in deciphering how cells communicate within intricate landscape and over long distance to establish precise gradients of signaling molecules that pattern many organs during vertebrate development. . For decades, most classical textbooks have conceptualized such signaling proteins as ?diffusible? molecules, known as morphogens, that transverse many cell diameters to pattern a field of cells. Recently, our lab, using a novel high resolution live imaging method, showed that, in the vertebrate limb, all cells extend very long and thin actin-based cellular protrusions termed specialized filopodia that connect cells over long distance. Moreover, they showed that a morphogen, Sonic Hedgehog, can travel along this meshwork of filopodia and hypothesize that morphogen transport through filopodia could account for the precise formation of morphogen gradients that pattern the limb bud. These filopodia are actin-based thus the main challenge is to be able to manipulate them without affecting the rest of the actin cytoskeleton. Currently, by combining live cell imaging, bioengineering and optogenetic I am trying to precisely manipulate these filopodia (modify size, orientation, formation) to directly assess their function in long-range cell communication and signaling gradient establishment.

Lab Affiliations


Publications

Journal Articles


  • Hox genes control vertebrate body elongation by collinear Wnt repression ELIFE Denans, N., Iimura, T., Pourquie, O. 2015; 4

    Abstract

    In vertebrates, the total number of vertebrae is precisely defined. Vertebrae derive from embryonic somites that are continuously produced posteriorly from the presomitic mesoderm (PSM) during body formation. We show that in the chicken embryo, activation of posterior Hox genes (paralogs 9-13) in the tail-bud correlates with the slowing down of axis elongation. Our data indicate that a subset of progressively more posterior Hox genes, which are collinearly activated in vertebral precursors, repress Wnt activity with increasing strength. This leads to a graded repression of the Brachyury/T transcription factor, reducing mesoderm ingression and slowing down the elongation process. Due to the continuation of somite formation, this mechanism leads to the progressive reduction of PSM size. This ultimately brings the retinoic acid (RA)-producing segmented region in close vicinity to the tail bud, potentially accounting for the termination of segmentation and axis elongation.

    View details for DOI 10.7554/eLife.04379

    View details for Web of Science ID 000350214500002

    View details for PubMedID 25719209

  • A random cell motility gradient downstream of FGF controls elongation of an amniote embryo NATURE Benazeraf, B., Francois, P., Baker, R. E., Denans, N., Little, C. D., Pourquie, O. 2010; 466 (7303): 248-252

    Abstract

    Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient, which has been implicated in the control of cell motility in this tissue. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements.

    View details for DOI 10.1038/nature09151

    View details for Web of Science ID 000279580800039

    View details for PubMedID 20613841

  • Real-Time Observation of Wnt beta-Catenin Signaling in the Chick Embryo DEVELOPMENTAL DYNAMICS Rios, A. C., Denans, N., Marcelle, C. 2010; 239 (1): 346-353

    Abstract

    A critical mediator of cell-cell signaling events during embryogenesis is the highly conserved Wnt family of secreted proteins. Reporter constructs containing multimerized TCF DNA binding sites have been used to detect Wnt beta-catenin dependent activity during animal development. In this report, we have constructed and compared several TCF green fluorescent protein (GFP) reporter constructs. They contained 3, 8, or 12 TCF binding sites upstream of a minimal promoter driving native or destabilized enhanced GFP (EGFP). We have used the electroporation of somites in the chick embryo as a paradigm to test them in vivo. We have verified that they all respond to Wnt signaling in vivo. We have then assessed their efficiency at reflecting the activity of the Wnt pathway. Using destabilized EGFP reporter constructs, we show that somite cells dynamically regulate Wnt/beta-catenin-dependent signaling, a finding that was confirmed by performing time-lapse video confocal observation of electroporated embryos.

    View details for DOI 10.1002/dvdy.22174

    View details for Web of Science ID 000273703900031

    View details for PubMedID 20014451

  • ESTABLISHMENT OF HOX VERTEBRAL IDENTITIES IN THE EMBRYONIC SPINE PRECURSORS HOX GENES Iimura, T., Denans, N., Pourquie, O. 2009; 88: 201-?

    Abstract

    The vertebrate spine exhibits two striking characteristics. The first one is the periodic arrangement of its elements-the vertebrae-along the anteroposterior axis. This segmented organization is the result of somitogenesis, which takes place during organogenesis. The segmentation machinery involves a molecular oscillator-the segmentation clock-which delivers a periodic signal controlling somite production. During embryonic axis elongation, this signal is displaced posteriorly by a system of traveling signaling gradients-the wavefront-which depends on the Wnt, FGF, and retinoic acid pathways. The other characteristic feature of the spine is the subdivision of groups of vertebrae into anatomical domains, such as the cervical, thoracic, lumbar, sacral, and caudal regions. This axial regionalization is controlled by a set of transcription factors called Hox genes. Hox genes exhibit nested expression domains in the somites which reflect their linear arrangement along the chromosomes-a property termed colinearity. The colinear disposition of Hox genes expression domains provides a blueprint for the regionalization of the future vertebral territories of the spine. In amniotes, Hox genes are activated in the somite precursors of the epiblast in a temporal colinear sequence and they were proposed to control their progressive ingression into the nascent paraxial mesoderm. Consequently, the positioning of the expression domains of Hox genes along the anteroposterior axis is largely controlled by the timing of Hox activation during gastrulation. Positioning of the somitic Hox domains is subsequently refined through a crosstalk with the segmentation machinery in the presomitic mesoderm. In this review, we focus on our current understanding of the embryonic mechanisms that establish vertebral identities during vertebrate development.

    View details for DOI 10.1016/S0070-2153(09)88007-1

    View details for Web of Science ID 000268505300007

    View details for PubMedID 19651306

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