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Rojas-Cervellera V.,Computer Simulation and Modeling Laboratory | Rojas-Cervellera V.,Institute Of Quimica Teorica I Computacional | Rojas-Cervellera V.,University of Barcelona | Giralt E.,Institute Of Recerca Biomedica Of Barcelona | And 5 more authors.
Inorganic Chemistry | Year: 2012

Recent structural determinations have shown that thiolate-protected gold nanoparticles are not as regular and symmetric as initially thought, but characteristic substructures (staple motifs) are formed on their surface. However, their mechanism of formation, especially the fate of the sulfur protons upon thiol binding, remains one of the most intriguing unanswered questions in gold cluster chemistry. By means of ab initio molecular dynamics (AIMD), we monitor the trajectory of thiol protons reacting with a gold cluster, demonstrating that the staple motif forms in a multiple-pathway chemical reaction, releasing molecular hydrogen. The results obtained also reconcile the conclusions of structural determinations with the interpretations of spectroscopic experiments on solution, suggesting the presence of intact thiols or chemisorbed hydrogen. © 2012 American Chemical Society.


Fonfria-Subiros E.,Polytechnic University of Catalonia | Acosta-Reyes F.,Polytechnic University of Catalonia | Saperas N.,Polytechnic University of Catalonia | Pous J.,Institute Of Recerca Biomedica Of Barcelona | And 2 more authors.
PLoS ONE | Year: 2012

We present here for the first time the crystal structure of an AT-hook domain. We show the structure of an AT-hook of the ubiquitous nuclear protein HMGA1, combined with the oligonucleotide d(CGAATTAATTCG)2, which has two potential AATT interacting groups. Interaction with only one of them is found. The structure presents analogies and significant differences with previous NMR studies: the AT-hook forms hydrogen bonds between main-chain NH groups and thymines in the minor groove, DNA is bent and the minor groove is widened. © 2012 Fonfría-Subirós et al.


Djabrayan N.J.-V.,Institute Of Biologia Molecular Of Barcelona Csic | Djabrayan N.J.-V.,Institute Of Recerca Biomedica Of Barcelona | Cruz J.,Institute Of Biologia Molecular Of Barcelona Csic | Cruz J.,Institute Of Biologia Evolutiva Csic Upf | And 5 more authors.
Cell Reports | Year: 2014

A population of Drosophila adult tracheal progenitor cells arises from differentiated cells of the larval main trachea that retain the ability to reenter the cell cycle and give rise to the multiple adult tracheal cell types. These progenitors are unique to the second tracheal metamere as homologous cells from other segments, express fizzy-related (fzr), the Drosophila homolog of CDH1 protein of the APC complex, and enter endocycle and do not contribute to adult trachea. Here, we examine the mechanisms for their quiescence and show that they reenter the cell cycle by expression of string/cdc25 through ecdysone. Furthermore, we show that preventing endocycle entry is both necessary and sufficient for these tracheal cells to exhibit markers of adult progenitors, thus modifying their genetic program. Finally, we show that Hox-mediated regulation of fzr expression is responsible for progenitor identity and thus specifies a group of differentiated cells with facultative stem cell features. © 2014 The Authors.


Campbell K.,Institute Of Biologia Molecular Of Barcelona Csic | Campbell K.,Institute Of Recerca Biomedica Of Barcelona | Whissell G.,Institute Of Recerca Biomedica Of Barcelona | Franch-Marro X.,Institute Of Biologia Evolutiva Csic Upf | And 4 more authors.
Developmental Cell | Year: 2011

The epithelial-to-mesenchymal transition (EMT) converts cells from static epithelial to migratory mesenchymal states (Hay, 1995). Here, we demonstrate that EMT in the Drosophila endoderm is dependent on the GATA-factor Serpent (Srp), and that Srp acts as a potent trigger for this transition when activated ectopically. We show that Srp affects endodermal-EMT through a downregulation of junctional dE-Cadherin (dE-Cad) protein, without a block in its transcription. Moreover, the relocalization of dE-Cad is achieved through the direct repression of crumbs (crb) by Srp. Finally, we show that hGATA-6, an ortholog of Srp, induces a similar transition in mammalian cells. Similar to Srp, hGATA-6 acts through the downregulation of junctional E-Cad, without blocking its transcription, and induces the repression of a Crumbs ortholog, crb2. Together, these results identify a set of GATA factors as a conserved alternative trigger to repress epithelial characteristics and confer migratory capabilities on epithelial cells in development and pathogenesis. © 2011 Elsevier Inc.


Brodu V.,French National Center for Scientific Research | Baffet A.D.,French National Center for Scientific Research | Le Droguen P.-M.,French National Center for Scientific Research | Casanova J.,Institute Of Biologia Molecular Of Barcelona Csic | And 2 more authors.
Developmental Cell | Year: 2010

Microtubules (MTs) are essential for many cell features, such as polarity, motility, shape, and vesicle trafficking. Therefore, in a multicellular organism, their organization differs between cell types and during development; however, the control of this process remains elusive. Here, we show that during Drosophila tracheal morphogenesis, MT reorganization is coupled to relocalization of the microtubule organizing centers (MTOC) components from the centrosome to the apical cell domain from where MTs then grow. We reveal that this process is controlled by the trachealess patterning gene in a two-step mechanism. MTOC components are first released from the centrosome by the activity of the MT-severing protein Spastin, and then anchored apically through the transmembrane protein Piopio. We further show that these changes are essential for tracheal development, thus stressing the functional relevance of MT reorganization for morphogenesis. © 2010 Elsevier Inc.


Campbell K.,Institute Of Biologia Molecular Of Barcelona Csic | Campbell K.,Institute Of Recerca Biomedica Of Barcelona | Casanova J.,Institute Of Biologia Molecular Of Barcelona Csic | Casanova J.,Institute Of Recerca Biomedica Of Barcelona
Nature Communications | Year: 2015

Collective cell migration is a key process underlying the morphogenesis of many organs as well as tumour invasion, which very often involves heterogeneous cell populations. Here we investigated how such populations can migrate cohesively in the Drosophila posterior midgut, comprised of epithelial and mesenchymal cells and show a novel role for the epithelial adhesion molecule E-cadherin (E-Cad) in mesenchymal cells. Despite a lack of junctions at the ultrastructure level, reducing E-Cad levels causes mesenchymal cells to detach from one another and from neighbouring epithelial cells; as a result, coordination between the two populations is lost. Moreover, Bazooka and recycling mechanisms are also required for E-Cad accumulation in mesenchymal cells. These results indicate an active role for E-Cad in mediating cohesive and ordered migration of non-epithelial cells, and discount the notion of E-Cad as just an epithelial feature that has to be switched off to enable migration of mesenchymal cells. © 2015 Macmillan Publishers Limited. All rights reserved.


Lebreton G.,Institute Of Biologia Molecular Of Barcelona Csic | Lebreton G.,Institute Of Recerca Biomedica Of Barcelona | Casanova J.,Institute Of Biologia Molecular Of Barcelona Csic | Casanova J.,Institute Of Recerca Biomedica Of Barcelona
Journal of Cell Science | Year: 2014

The role of tip and rear cells in collective migration is still a matter of debate and their differences at the cytoskeletal level are poorly understood. Here, we analysed these issues in the Drosophila trachea, an organ that develops from the collective migration of clusters of cells that respond to Branchless (Bnl), a fibroblast growth factor (FGF) homologue expressed in surrounding tissues. We track individual cells in the migratory cluster and characterise their features and unveil two prototypical types of cytoskeletal organisation that account for tip and rear cells respectively. Indeed, once the former are specified, they remain as such throughout migration. Furthermore, we show that FGF signalling in a single tip cell can trigger the migration of the cells in the branch. Finally, we found specific Rac activation at the tip cells and analysed how FGF-independent cell features, such as adhesion and motility, act on coupling the behaviour of trailing and tip cells. Thus, the combined effect of FGF promoting leading cell behaviour and the modulation of cell properties in a cluster can account for the wide range of migratory events driven by FGF. © 2014. Published by The Company of Biologists Ltd.


Gervais L.,Institute Of Biologia Molecular Of Barcelona Csic | Gervais L.,Institute Of Recerca Biomedica Of Barcelona | Casanova J.,Institute Of Biologia Molecular Of Barcelona Csic | Casanova J.,Institute Of Recerca Biomedica Of Barcelona
Current Biology | Year: 2010

Fine tubes form inside cells as they reach their target tissues in epithelial ducts and in angiogenesis [1-4]. Although a very suggestive model of cell hollowing proposes that intracellular lumen could arise by coalescence of intracellular vacuoles [5, 6], how those tubes form in vivo remains an open question. We addressed this issue by examining intracellular lumen formation in the Drosophila trachea. The main branches of the Drosophila tracheal system have an extracellular lumen because their cells fold to form a tube [7]. However, terminal cells, specialized cells in some of the main branches, form unicellular branches by the generation of an intracellular lumen [8]. Conversely to the above-mentioned model, we find that the intracellular lumen arises by growth of an apical membrane inwards the cell. In support, we detect an appropriate subcellular compartmentalization of different components of the intracellular trafficking machinery. We show that both cellular elongation and lumen formation depend on a mechanism based on asymmetric actin accumulation and microtubule network organization. Given the similarities in the formation of fine respiratory tubes and capillaries, we propose that an inward membrane growth model could account for lumen formation in both processes. © 2010 Elsevier Ltd. All rights reserved.


Campbell K.,Institute Of Biologia Molecular Of Barcelona Csic | Campbell K.,Institute Of Recerca Biomedica Of Barcelona | Casanova J.,Institute Of Biologia Molecular Of Barcelona Csic | Casanova J.,Institute Of Recerca Biomedica Of Barcelona | Skaer H.,University of Cambridge
Mechanisms of Development | Year: 2010

The intercalation of mesenchymal cells into epithelia, through mesenchymal-to-epithelial transition (MET), underlies organogenesis, for example, in nephrogenesis, and tissue regeneration, during cell renewal and wound repair. Despite its importance, surprisingly little is known about the mechanisms that bring about MET in comparison with the related and much-studied, reverse process, epithelial-to-mesenchymal transition (EMT). We analyse the molecular events that regulate MET as stellate cells integrate into the established epithelium of the developing renal tubules in Drosophila. We show that stellate cells polarise as they integrate between epithelial principal cells and that the normal, localised expression of cell polarity proteins in principal cells is required for stellate cells to become epithelial. While the basolateral and apical membranes act as cues for stellate cell polarity, adherens junction integrity is required to regulate their movement through the epithelium; in the absence of these junctions stellate cells continue migrating into the tubule lumen. We also show that expression of basolateral proteins in stellate cells is a prerequisite for their ingression between principal cells. We present a model in which the contacts with successive principal cell membrane domains made by stellate cells as they integrate between them act as a cue for the elaboration of stellate cell polarity. We suggest that the formation of zonula adherens junctions between new cell neighbours establishes their apico-basal positions and stabilises them in the epithelium. © 2010 Elsevier Ireland Ltd.


Gervais L.,Institute Of Biologia Molecular Of Barcelona | Gervais L.,Institute Of Recerca Biomedica Of Barcelona | Casanova J.,Institute Of Biologia Molecular Of Barcelona | Casanova J.,Institute Of Recerca Biomedica Of Barcelona
Development | Year: 2011

Recent data have demonstrated a crucial role for the transcription factor SRF (serum response factor) downstream of VEGF and FGF signalling during branching morphogenesis. This is the case for sprouting angiogenesis in vertebrates, axonal branching in mammals and terminal branching of the Drosophila tracheal system. However, the specific functions of SRF in these processes remain unclear. Here, we establish the relative contributions of the Drosophila homologues of FGF [Branchless (BNL)] and SRF [Blistered (BS)] in terminal tracheal branching. Conversely to an extended view, we show that BNL triggers terminal branching initiation in a DSRF-independent mechanism and that DSRF transcription induced by BNL signalling is required to maintain terminal branch elongation. Moreover, we report that increased and continuous FGF signalling can trigger tracheal cells to develop full-length terminal branches in the absence of DSRF transcription. Our results indicate that DSRF acts as an amplifying step to sustain the progression of terminal branch elongation even in the wild-type conditions of FGF signalling. © 2011. Published by The Company of Biologists Ltd.

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