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Le Dreau G.,Institute Biologia Molecular Of Barcelona | Marti E.,Institute Biologia Molecular Of Barcelona
Cellular and Molecular Life Sciences | Year: 2013

Bone morphogenetic proteins (BMPs) are one of the main classes of multi-faceted secreted factors that drive vertebrate development. A growing body of evidence indicates that BMPs contribute to the formation of the central nervous system throughout its development, from the initial shaping of the neural primordium to the generation and maturation of the different cell types that form the functional adult nervous tissue. In this review, we focus on the multiple activities of BMPs during spinal cord development, paying particular attention to recent results that highlight the complexity of BMP signaling during this process. These findings emphasize the unique capacity of these signals to mediate various functions in the same tissue throughout development, recruiting diverse effectors and strategies to instruct their target cells. © 2013 European Union.


Lesage B.,Barcelona Institute for Research in Biomedicine | Gutierrez I.,Institute Biologia Molecular Of Barcelona | Marti E.,Institute Biologia Molecular Of Barcelona | Gonzalez C.,Barcelona Institute for Research in Biomedicine | Gonzalez C.,Catalan Institution for Research and Advanced Studies
Current Opinion in Genetics and Development | Year: 2010

Drosophila neuroblasts and mouse radial glial cells can divide asymmetrically to self-renew while producing differentiating daughter cells that contribute to brain growth. Intense research activity in the past few years has started to unveil some of the processes that govern asymmetric division in these two cell types. Here we discuss the case of centrosome asymmetry and the contribution of spindle orientation and non-spindle-related centrosome functions. Although still fragmentary, the emerging picture suggests that both notable parallelisms and striking differences apply. © 2010 Elsevier Ltd.


Ulloa F.,Barcelona Institute for Research in Biomedicine | Marti E.,Institute Biologia Molecular Of Barcelona
Developmental Dynamics | Year: 2010

The spinal cord has been used as a model to dissect the mechanisms that govern the patterning of tissues during animal development, since the principles that rule the dorso-ventral patterning of the neural tube are applicable to other systems. Signals that determine the dorso-ventral axis of the spinal cord include Sonic hedgehog (Shh), acting as a bona fide morphogenetic signal to determine ventral progenitor identities, and members of the Bmp and the Wnt families, acting in the dorsal neural tube. Although Wnts have been initially recognized as important in proliferation of neural progenitor cells, their role in the dorso-ventral patterning has been controversial. In this review, we discuss recent reports that show an important contribution of the Wnt canonical pathway in dorso-ventral pattern formation. These data allow building a model by which the ventralizing activity of Shh is antagonized by Wnt activity through the expression of Gli3, a potent inhibitor of the Shh pathway. Therefore, antagonistic interactions between canonical Wnt, promoting dorsal identities, and Shh pathways, inducing ventral ones, would define the dorso-ventral patterning of the developing central nervous system. © 2009 Wiley-Liss, Inc.


Thomson T.M.,Institute Biologia Molecular Of Barcelona | Guerra-Rebollo M.,Institute Biologia Molecular Of Barcelona
Biochemical Society Transactions | Year: 2010

The repair of lesions and gaps in DNA follows different pathways, each mediated by specific proteins and complexes. Post-translational modifications in many of these proteins govern their activities and interactions, ultimately determining whether a particular pathway is followed. Prominent among these modifications are the addition of phosphate or ubiquitin (and ubiquitin-like) moieties that confer new binding surfaces and conformational states on the modified proteins. The present review summarizes some of consequences of ubiquitin and ubiquitin-like modifications and interactions that regulate nucleotide excision repair, translesion synthesis, double-strand break repair and interstrand cross-link repair, with the discussion of relevant examples in each pathway. © The Authors Journal compilation.


Mansilla S.,Institute Biologia Molecular Of Barcelona | Llovera L.,Institute Biologia Molecular Of Barcelona | Portugal J.,Institute Biologia Molecular Of Barcelona
Anti-Cancer Agents in Medicinal Chemistry | Year: 2012

Cell death plays an important role in cancer growth and progression, as well as in the efficiency of chemotherapy. Although apoptosis is commonly regarded as the principal mechanism of programmed cell death, it has been increasingly reported that several anticancer agents do not only induce apoptosis but other forms of cell death such as necrosis, autophagy and mitotic catastrophe, as well as the state of permanent loss of proliferative capacity known as senescence. A deeper understanding of what we know about chemotherapyinduced death is rather relevant considering the emerging knowledge of non-apoptotic cell death signaling pathways, and the fact that many tumors have the apoptosis pathway seriously compromised. In this review we examine the effects that various anti-cancer agents have on pathways involved in the different cell death outcomes. Novel and specific anti-cancer agents directed toward members of the cell death signaling pathways are being developed and currently being tested in clinical trials. If we precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, we might succeed in more effective and less toxic chemotherapy. © 2012 Bentham Science Publishers.


Roca J.,Institute Biologia Molecular Of Barcelona
Chromosoma | Year: 2011

Virtually all processes of the genome biology affect or are affected by the torsional state of DNA. Torsional energy associated with an altered twist facilitates or hinders the melting of the double helix, its molecular interactions, and its spatial folding in the form of supercoils. Yet, understanding how the torsional state of DNA is modulated remains a challenging task due to the multiplicity of cellular factors involved in the generation, transmission, and dissipation of DNA twisting forces. Here, an overview of the implication of DNA topoisomerases, DNA revolving motors, and other DNA interactions that determine local levels of torsional stress in bacterial and eukaryotic chromosomes is provided. Particular emphasis is made on the experimental approaches being developed to assess the torsional state of intracellular DNA and its organization into topological domains. © Springer-Verlag 2011.


Vizcaino C.,Institute Biologia Molecular Of Barcelona | Mansilla S.,Institute Biologia Molecular Of Barcelona | Portugal J.,Institute Biologia Molecular Of Barcelona
Pharmacology and Therapeutics | Year: 2015

Sp1 (specificity protein 1) is a well-known member of a family of transcription factors that also includes Sp2, Sp3 and Sp4, which are implicated in an ample variety of essential biological processes and have been proven important in cell growth, differentiation, apoptosis and carcinogenesis. Sp1 activates the transcription of many cellular genes that contain putative CG-rich Sp-binding sites in their promoters. Sp1 and Sp3 proteins bind to similar, if not the same, DNA tracts and compete for binding, thus they can enhance or repress gene expression. Evidences exist that the Sp-family of proteins regulates the expression of genes that play pivotal roles in cell proliferation and metastasis of various tumors. In patients with a variety of cancers, high levels of Sp1 protein are considered a negative prognostic factor. A plethora of compounds can interfere with the trans-activating activities of Sp1 and other Sp proteins on gene expression. Several pathways are involved in the down-regulation of Sp proteins by compounds with different mechanisms of action, which include not only the direct interference with the binding of Sp proteins to their putative DNA binding sites, but also promoting the degradation of Sp protein factors. Down-regulation of Sp transcription factors and Sp1-regulated genes is drug-dependent and it is determined by the cell context. The acknowledgment that several of those compounds are safe enough might accelerate their introduction into clinical usage in patients with tumors that over-express Sp1. © 2015 Elsevier Ltd. All rights reserved.


Estaras C.,Institute Biologia Molecular Of Barcelona
Development (Cambridge, England) | Year: 2012

Neural development requires crosstalk between signaling pathways and chromatin. In this study, we demonstrate that neurogenesis is promoted by an interplay between the TGFβ pathway and the H3K27me3 histone demethylase (HDM) JMJD3. Genome-wide analysis showed that JMJD3 is targeted to gene promoters by Smad3 in neural stem cells (NSCs) and is essential to activate TGFβ-responsive genes. In vivo experiments in chick spinal cord revealed that the generation of neurons promoted by Smad3 is dependent on JMJD3 HDM activity. Overall, these findings indicate that JMJD3 function is required for the TGFβ developmental program to proceed.


Saade M.,Institute Biologia Molecular Of Barcelona | Gutierrez-Vallejo I.,Institute Biologia Molecular Of Barcelona | LeDreau G.,Institute Biologia Molecular Of Barcelona | Rabadan M.A.,Institute Biologia Molecular Of Barcelona | And 3 more authors.
Cell Reports | Year: 2013

The different modes of stem cell division are tightly regulated to balance growth and differentiation during organ development and homeostasis, and these regulatory processes are subverted in tumor formation. Here, we developed markers that provided the single-cell resolution necessary to quantify the three modes of division taking place in the developing nervous system invivo: self-expanding, PP; self-replacing, PN; and self-consuming, NN. Using these markers and a mathematical model that predicts the dynamics of motor neuron progenitor division, we identify a role for the morphogen Sonic hedgehog in the maintenance of stem cell identity in the developing spinal cord. Moreover, our study provides insight into the process linking lineage commitment to neurogenesis with changes in cell-cycle parameters. As a result, we propose a challenging model in which the external Sonic hedgehog signal dictates stem cell identity, reflected in the consequent readjustment of cell-cycle parameters


Roca J.,Institute Biologia Molecular Of Barcelona
Transcription | Year: 2011

Most genome transactions are favored by DNA (-) torsional stress, i.e. unconstrained unwinding or supercoiling of DNA. A question raised here is whether DNA (+) torsional stress, which precludes DNA unwinding, could be also relevant in gene regulation. Such DNA twist dynamics could be determined by chromatin architecture.

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