Answer added in Genetics30 Does anyone have any knowledge/reference about transcriptional activator which also acts as a repressor?By Yohanes Kurniawan · Osaka UniversityEumorphia Remboutsika · Biomedical Sciences Research Center Alexander FlemingDear yohanes , I protein we worked on called leu3p in yeast has the duality properties you are asking for. You will your answers to Poulou et al. 2010... [more]Dear yohanes , I protein we worked on called leu3p in yeast has the duality properties you are asking for. You will your answers to Poulou et al. 2010 PLOs One. Let me know if I can be of any more help.Following
Article: Application of a novel strategy of engineering conditional alleles to a single exon gene, sox2.Nikolaos Mandalos, Marannia Saridaki, Jessica Lea Harper, Anastasia Kotsoni, Peter Yang, Aris N Economides, Eumorphia Remboutsika[show abstract] [hide abstract]
ABSTRACT: The Conditional by Inversion (COIN) method for engineering conditional alleles relies on an invertible optimized gene trap-like element, the COIN module, for imparting conditionality. The COIN module contains an optimized 3' splice site-polyadenylation signal pair, but is inserted antisense to the target gene and therefore does not alter transcription, until it is inverted by Cre recombinase. In order to make COIN applicable to all protein-coding genes, the COIN module has been engineered within an artificial intron, enabling insertion into an exon. Therefore, theoretically, the COIN method should be applicable to single exon genes, and to test this idea we engineered a COIN allele of Sox2. This single exon gene presents additional design challenges, in that its proximal promoter and coding region are entirely contained within a CpG island, and are also spanned by an overlapping transcript, Sox2Ot, which contains mmu-miR1897. Here, we show that despite disruption of the CpG island by the COIN module intron, the COIN allele of Sox2 (Sox2(COIN)) is phenotypically wild type, and also does not interfere with expression of Sox2Ot and miR1897. Furthermore, the inverted COIN allele of Sox2, Sox2(INV) is functionally null, as homozygotes recapitulate the phenotype of Sox2(ßgeo/ßgeo) mice, a well-characterized Sox2 null. Lastly, the benefit of the eGFP marker embedded in the COIN allele is demonstrated as it mirrors the expression pattern of Sox2. Our results demonstrate the applicability of the COIN technology as a method of choice for targeting single exon genes.PLoS ONE 01/2012; 7(9):e45768. · 4.09 Impact Factor
Article: Bmp7 regulates the survival, proliferation, and neurogenic properties of neural progenitor cells during corticogenesis in the mouse.Aikaterini Segklia, Eve Seuntjens, Maximilianos Elkouris, Sotiris Tsalavos, Elke Stappers, Thimios A Mitsiadis, Danny Huylebroeck, Eumorphia Remboutsika, Daniel Graf[show abstract] [hide abstract]
ABSTRACT: Bone morphogenetic proteins (BMPs) are considered important regulators of neural development. However, results mainly from a wide set of in vitro gain-of-function experiments are conflicting since these show that BMPs can act either as inhibitors or promoters of neurogenesis. Here, we report a specific and non-redundant role for BMP7 in cortical neurogenesis in vivo using knockout mice. Bmp7 is produced in regions adjacent to the developing cortex; the hem, meninges, and choroid plexus, and can be detected in the cerebrospinal fluid. Bmp7 deletion results in reduced cortical thickening, impaired neurogenesis, and loss of radial glia attachment to the meninges. Subsequent in vitro analyses of E14.5 cortical cells revealed that lack of Bmp7 affects neural progenitor cells, evidenced by their reduced proliferation, survival and self-renewal capacity. Addition of BMP7 was able to rescue these proliferation and survival defects. In addition, at the developmental stage E14.5 Bmp7 was also required to maintain Ngn2 expression in the subventricular zone. These data demonstrate a novel role for Bmp7 in the embryonic mouse cortex: Bmp7 nurtures radial glia cells and regulates fundamental properties of neural progenitor cells that subsequently affect Ngn2-dependent neurogenesis.PLoS ONE 01/2012; 7(3):e34088. · 4.09 Impact Factor
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ABSTRACT: Lung development is controlled by regulatory networks governing mesenchymal-epithelial interactions. Transcription factors and signaling molecules are known to participate in this process, yet little is known about the post-transcriptional regulation of these networks. Here we demonstrate that the RNA-binding protein (RBP) HuR is an essential regulator of mesenchymal responses during lung branching. Its epiblast-induced deletion blocked the morphogenesis of distal bronchial branches at the initiation of the pseudoglandular stage. The phenotype originated from defective mesenchymal responses since the conditional restriction of HuR deletion in epithelial progenitors did not affect distal branching or the completion of lung maturation. The loss of HuR resulted in the reduction of the key inducer of bud outgrowth and endodermal branching, FGF10 and one of its putative transcriptional regulators, Tbx4. Furthermore, exogenous FGF10 could rescue the branching defect of affected lung buds. HuR was found to bind and control the Fgf10 and Tbx4 mRNAs; as a result its deletion abolished their inducible post-transcriptional regulation by the mesenchymal regulator FGF9. Our data reveals HuR as the first RBP identified to play a dominant role in lung development and as a key post-transcriptional regulator of networks guiding tissue remodeling during branching morphogenesis.Developmental Biology 06/2011; 354(2):267-79. · 4.07 Impact Factor
Article: Flexibility of neural stem cells.Eumorphia Remboutsika, Maximilianos Elkouris, Angelo Iulianella, Cynthia L Andoniadou, Maria Poulou, Thimios A Mitsiadis, Paul A Trainor, Robin Lovell-Badge[show abstract] [hide abstract]
ABSTRACT: Embryonic cortical neural stem cells are self-renewing progenitors that can differentiate into neurons and glia. We generated neurospheres from the developing cerebral cortex using a mouse genetic model that allows for lineage selection and found that the self-renewing neural stem cells are restricted to Sox2 expressing cells. Under normal conditions, embryonic cortical neurospheres are heterogeneous with regard to Sox2 expression and contain astrocytes, neural stem cells, and neural progenitor cells sufficiently plastic to give rise to neural crest cells when transplanted into the hindbrain of E1.5 chick and E8 mouse embryos. However, when neurospheres are maintained under lineage selection, such that all cells express Sox2, neural stem cells maintain their Pax6(+) cortical radial glia identity and exhibit a more restricted fate in vitro and after transplantation. These data demonstrate that Sox2 preserves the cortical identity and regulates the plasticity of self-renewing Pax6(+) radial glia cells.Frontiers in physiology. 01/2011; 2:16.
Article: Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis.Maximilianos Elkouris, Nikos Balaskas, Maria Poulou, Panagiotis K Politis, Elena Panayiotou, Stavros Malas, Dimitra Thomaidou, Eumorphia Remboutsika[show abstract] [hide abstract]
ABSTRACT: Neural stem/progenitor cells maintain their identity via continuous self-renewal and suppression of differentiation. Gain-of-function experiments in the chick revealed an involvement for Sox1-3 transcription factors in the maintenance of the undifferentiated neural progenitor (NP) identity. However, the mechanism(s) employed by each factor has not been resolved. Here, we derived cortical neural/stem progenitor cells from wild-type and Sox1-null mouse embryos and found that Sox1 plays a key role in the suppression of neurogenic cell divisions. Loss of Sox1 leads to progressive depletion of self-renewing cells, elongation of the cell cycle of proliferating cells, and significant increase in the number of cells exiting the cell cycle. In proliferating NP cells, Sox1 acts via a prospero-related homeobox 1 (Prox1)-mediated pathway to block cell cycle exit that leads to neuronal differentiation in vivo and in vitro. Thus, our results demonstrate that Sox1 regulates the size of the cortical NP pool via suppression of Prox1-mediated neurogenic cell divisions.Stem Cells 01/2011; 29(1):89-98. · 7.78 Impact Factor
Understanding the mechanisms by which stem cells arise and guard their identity is crucial for proper embryonic development, tissue and organ regeneration as well as tumour suppression. Research in our laboratory aims to understand how stem cells acquire and maintain their tissue-specific identity and potency.