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)
License, Universite D'Aix-Marseille Ii (2005)
Master of Science, Universite D'Aix-Marseille Ii (2007)
Doctorat, Universite De Strasbourg (2011)
Maria Barna, Postdoctoral Faculty Sponsor
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.
Maria Barna, (5/2/2014)
Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2015; 112 (35): E4884-E4893
The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3' UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae.
View details for DOI 10.1073/pnas.1512655112
View details for Web of Science ID 000360383200011
View details for PubMedID 26283362
Hox genes control vertebrate body elongation by collinear Wnt repression
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
2010; 466 (7303): 248-252
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
2010; 239 (1): 346-353
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
2009; 88: 201-?
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