Junko Odajima,
Zachary P Wills,
Yasmine M Ndassa,
Miho Terunuma,
Karla Kretschmannova,
Tarek Z Deeb,
Yan Geng,
Sylwia Gawrzak,
Isabel M Quadros,
Jennifer Newman,
Manjusri Das,
Marie E Jecrois,
Qunyan Yu,
Na Li,
Frederic Bienvenu,
Stephen J Moss,
Michael E Greenberg,
Jarrod A Marto and
Piotr Sicinski
Abstract
We use a combination of in vivo quantitative proteomics and analyses of cyclin E knockout mice to demonstrate that in terminally differentiated neurons cyclin E forms complexes with Cdk5 and controls synapse function by restraining Cdk5 activity. Ablation of cyclin E led to a decreased number of s...
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PMID: 21944720
PDF is available here.
Abstract
We show that Fgf8 and Sema3f, produced by early dental epithelium, respectively, attract and repulse mesenchymal cells, which cause them to pack tightly together during mouse tooth development. Resulting mechanical compaction-induced changes in cell shape induce odontogenic transcription factors (Pa...
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PMID: 21924961
PDF is available here.
Abstract
Embryonic stem (ES) cells are pluripotent cells isolated from an early embryo and grown as a cell line in tissue culture. Their discovery came from the conjunction of studies in human pathology, mouse genetics, early mouse embryo development, cell surface immunology and tissue cultur...
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PMID: 21941277
PDF is available here.
Abstract
We hypothesized that estrogen signals its effect on surfactant protein B (Sftpb) expression through interactions of ERβ and ErbB4. Estrogen and NRG treatment decreased cell numbers and stimulated Sftpb expression in type II cells. Estrogen and NRG both stimulated phosphorylation of ERβ and co-loca...
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PMID: 21777626
PDF is available here.
Abstract
We generated embryos in which smoothened (Smo), an essential transducer of Hedgehog (Hh) signaling, was conditionally inactivated in the otic epithelium (Smo(ecko)). Ventral otic derivatives failed to form in Smo(ecko) embryos, whereas vestibular structures developed properly. Consistent with these...
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PMID: 21831920
PDF is available here.
Abstract
We show that the epiblast-specific deletion of the gene encoding the BMP type 1 receptor (Acvr1) compromised development of nodal cilia, which results in defects in leftward fluid flow and, thus, abnormalities in left-right patterning. Acvr1 deficiency in mouse embryonic fibroblasts (MEFs) resulted...
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PMID: 21831921
PDF is available here.
Abstract
We generated mice (termed "Nes-Met") in which met is inactivated from midembryonic stages onward in the CNS only. Adult animals showed motor behavioral defects suggestive of impaired innervation of pectoral muscles. Correspondingly, in neonatal spinal cords of Nes-Met mutants, we observed death of a...
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PMID: 21813676
PDF is available here.
Abstract
We transduced SATB2 into murine adult stem cells, and found that SATB2 significantly increased expression levels of bone matrix proteins, osteogenic transcription factors, and a potent angiogenic factor, vascular endothelial growth factor. Using an osterix (Osx) promoter-luciferase construct and cal...
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PMID: 21385070
PDF is available here.
Calvin Simerly,
Dave McFarland,
Carlos Castro,
Chih-Cheng Lin,
Carrie Redinger,
Ethan Jacoby,
Jocelyn Mich-Basso,
Kyle Orwig,
Parker Mills,
Eric Ahrens,
Chris Navara and
Gerald Schatten
Abstract
Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst...
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PMID: 21543277
PDF is available here.
Abstract
We provide new data concerning changes in the spinal cord, neuromuscular junctions and muscle cells, and in the organs of the immune system. The expression of 10 synaptic proteins was analyzed in 3-dimensionally reconstructed neuromuscular junctions by confocal microscopy. In addition to defects in...
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PMID: 21572339
PDF is available here.
Abstract
The Zagreb Collection of developing and adult human brains was founded in 1974 by Ivica Kostović and consists of 1,278 developing and adult human brains, including 610 fetal, 317 children, and 359 adult brains. It is one of the largest collections of developing human brains. The col...
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PMID: 21599691
PDF is available here.
Abstract
We recently developed a new method termed VelociMouse for the production of F0-generation mice that are fully derived from gene-targeted ES cells. In the version of the VelociMouse method described here, laser ablation of a portion of the zona pellucid (zp) of a normal eight-cell-stage embryo facili...
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PMID: 19266341
PDF is available here.
Abstract
In vitro embryo production (IVP) suffers from excessive developmental failure. Its inefficiency is linked, in part, to reactive oxygen species (ROS) brought on by high ex vivo oxygen (O(2)) tensions. To further delineate the effects of ROS on IVP, the intracellular ROS levels of early bovine embryos...
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PMID: 21557923
PDF is available here.
Abstract
The involvement of protein oxidation in embryonic mortality (EM) has been poorly investigated in cows. Advanced oxidation protein products (AOPP) are markers of protein oxidation generated by activated neutrophils and involved in inflammation. The aim of this work was to study AOPP in cow plasma and...
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PMID: 21557919
PDF is available here.
Abstract
The aim of this study was to compare gene silencing in bovine zygotes when small interfering RNAs (siRNAs) were introduced into bovine zygotes by microinjection or lipid-based transfection. In Experiment 1, E-cadherin siRNA was injected at 100 or 375 µM and compared with PBS-injected and non-injecte...
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PMID: 21557920
PDF is available here.
Abstract
We conditionally inactivated the catalytic subunit α of PP2A (PP2Acα), which is the predominant form of PP2Ac, during early embryonic hematopoiesis. Loss of PP2Acα in hematopoietic cells perturbed definitive erythropoiesis characterized by fetal liver atrophy, reduced Ter119(+) cell number, abnor...
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PMID: 21514445
PDF is available here.
Abstract
We found a marked increase of 4-hydroxy-2-nonenal (4-HNE) adducts, a lipid peroxidation marker, in the caudate and putamen of HD brains and in the striatum of HD mice. Notably, 4-HNE immunoreactivity was colocalized with mutant huntingtin inclusions in the striatal neurons of R6/2 HD mice. Administr...
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PMID: 21161248
PDF is available here.
Abstract
We describe conditions for RA treatment of human embryonic stem cells that result in efficient differentiation to a heterogeneous population of GABAergic interneurons without the appearance of GABAergic striatal projection neurons, thus providing an in vitro method for generation of GABAergic intern...
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PMID: 21532733
PDF is available here.
Abstract
We examined the semiserial histology of 20 human embryos and fetuses (crown-rump length 11-40 mm). We started observations of the canal at the stage through which the lung bud extends far caudally along the dorsal body wall to the level of the future adrenal, and the phrenic nerve has already reache...
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PMID: 21370493
PDF is available here.
Abstract
We found that exposure of motor neurons to kainic acid produces intracellular changes associated with defective autophagy. In this experimental conditions, pharmacological activation of autophagy rescues the loss of motor neurons....
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PMID: 21412719
PDF is available here.
Abstract
We have identified the energy stress-inducing agent AICAR, the protein folding inhibitor 17-AAG, and the autophagy inhibitor chloroquine as exhibiting this property. AICAR induces p53-mediated apoptosis in primary mouse embryonic fibroblasts (MEFs) trisomic for chromosome 1, 13, 16, or 19. AICAR and...
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PMID: 21315436
PDF is available here.
Abstract
Stem cells make more of themselves by self-renewing cell divisions. In the February 1, 2011, issue of Genes & Development, Taoudi and colleagues (pp. 251-262) show an essential role for the ETS transcription factor ERG in the self-renewal of embryonic hematopoietic stem cells. A model is presented in...
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PMID: 21325129
PDF is available here.
Abstract
We demonstrate that Tbx6-dependent regulation of Sox2 determines the fate of axial stem cells. In wild-type embryos, enhancer N1 of the neural primordial gene Sox2 is activated in the caudal lateral epiblast, and the cells staying in the superficial layer sustain N1 activity and activate Sox2 expres...
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PMID: 21331042
PDF is available here.
Abstract
We present here differentiation of R1 embryonic stem (ES) cells into GABAergic dorsal spinal cord neurons by sequential treatment with developmental signaling molecules. We found that retinoic acid, Bmp4 altered the specification of neural progenitors and instructed neural fate when applied at disti...
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PMID: 21241191
PDF is available here.
Abstract
We investigated the reprogramming potential of enucleated and cryopreserved oocytes for the development of full-term cloned mice. BDF1 strain mouse oocytes were cryopreserved at metaphase II, before and after enucleation. After thawing, cumulus cell nuclei were microinjected to generate clones. Alth...
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PMID: 20964481
PDF is available here.
Abstract
We show that the kinesin-3 motor KIF16B/Rab14 complex acts in biosynthetic Golgi-to-endosome traffic of the fibroblast growth factor receptor (FGFR) during early embryonic development. Kif16b(-/-) mouse embryos failed in developing epiblast and primitive endoderm lineages and died in the peri-implan...
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PMID: 21238925
PDF is available here.
Abstract
We will discuss the position of IVM in the strategy of fertility preservation in young women....
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PMID: 21232880
PDF is available here.
Abstract
An omphalocele is one of the major ventral body wall malformations and is characterized by abnormally herniated viscera from the body trunk. It has been frequently found to be associated with other structural malformations, such as genitourinary malformations and digit abnormalities. In spite of its...
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PMID: 21283718
PDF is available here.
Abstract
We generated Pik3c3 null mice. We show here that Pik3c3 heterozygous are normal and fertile. In contrast, Pik3c3 homozygous mutants are embryonic lethal and die between E7.5 and E8.5 of embryogenesis. Mutant embryos are poorly developed with no evidence of mesoderm formation, and suffer from severel...
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PMID: 21283715
PDF is available here.
Abstract
We vitrified mouse oocytes using a range of concentrations of trehalose (0 to 0.3 M) and demonstrated that 0.1 and 0.3 M trehalose had similar developmental rates, which were significantly different to the 0.2 M cohort (P<0.05). As mitochondria are important for fertilisation outcome, we observed th...
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PMID: 21738724
PDF is available here.
Abstract
We identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers formi...
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PMID: 21304940
PDF is available here.
Abstract
We previously found a striking effect on coordination between the two dynein motor domains, resulting in a defect in dynein run length in vitro and in vivo....
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PMID: 21612657
PDF is available here.
Abstract
Mouse embryonic stem cells (mESCs) were first derived and cultured almost 30 years ago and ever since have been valuable tools for creating knockout mice and for studying early mammalian development. More recently (1998), human embryonic stem cells (hESCs) have been derived from blastocysts, and num...
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PMID: 21042983
PDF is available here.
Abstract
We have shown that hESCs can be stably transfected with a plasmid in which expression of the green fluorescent protein (GFP) is under the control of the Oct-4 promoter using chemical transfection. The expression pattern of transgenic Oct-4-GFP reflects that of endogenous Oct-4....
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PMID: 21042987
PDF is available here.
Abstract
We investigated the role of Spry1 in the development of the endothelial and hematopoietic lineages during development.
Quantitative RT-PCR analysis demonstrates that Spry1, Spry2, and Spry4 are expressed in Flk1(+) hemangioblasts in vivo, and decline significantly in c-Kit(+) and CD4...
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PMID: 21483770
PDF is available here.
Abstract
We report that ovarian cell lines VOSE, A2780, CP70, C200, OV202, OVCAR3, SKOV3ip, PE01 and PE04 predominantly express -α(1), -β(1), -γ(1) and -γ(2) isoforms of AMPK subunits. Our studies show that metformin treatment (1) significantly inhibited proliferation of diverse chemo-responsive and -res...
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PMID: 19874425
PDF is available here.
Abstract
We found that Tem1 gene expression was initially detectable in the dorsal aortic wall, the heart, the umbilical vessels, the first branchial arch, and the cephalic mesenchyme at E9.5. From E10.5 to E14.5, Tem1 gene expression was additionally seen mainly in the genital tubercle, the mesonephros, the...
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PMID: 21402174
PDF is available here.
Abstract
We report the neurotoxic effects of FTI-277 and the involvement of reactive oxygen species (ROS) in FTI-induced neurotoxicity. Although there is no significant effect of FTI-277 for 2 days, long-term treatment of FTI-277 for 4 days induced dramatic reduction in outgrowth, maturation and branching of...
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PMID: 21040708
PDF is available here.
Abstract
The rodent whole embryo culture (WEC) system is a well-established model for characterizing developmental toxicity of test compounds and conducting mechanistic studies. Laboratories have taken various approaches in describing type and severity of developmental findings of organogenes...
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PMID: 21058394
PDF is available here.
Abstract
We present an overview of the role of RA in the developing mammalian inner ear, discussing both how and when RA may act to critically control a program of inner ear development. Molecular mechanisms of otic teratogenicity involving two members of the fibroblast growth factor family, FGF3 and FGF10,...
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PMID: 21108385
PDF is available here.
Abstract
We have identified a novel mode of signaling pathway integration/coordination that occurs outside cells during development that involves an LDL receptor family member. Physical interaction between an extracellular protein (Wise) that binds BMP ligands and an Lrp receptor (Lrp4) that modulates Wnt si...
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PMID: 21108386
PDF is available here.
Abstract
During development, microvessels acquire specialized functions to meet the requirements of different tissues and organs. The vasculature of the brain constitutes one of the best examples of an organ-specific and highly specialized microvasculature, in which the endothelial cells that...
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PMID: 21084718
PDF is available here.
Abstract
We have now investigated the possible involvement of PiT1 in TNF-induced apoptosis. We show that PiT1-depleted cells are more sensitive to the proapoptotic activity of TNF (i.e. when the antiapoptotic NFκB pathway is inactivated). These observations were made in the human HeLa cancer cell line eith...
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PMID: 20817733
PDF is available here.
Seth S Margolis,
John Salogiannis,
David M Lipton,
Caleigh Mandel-Brehm,
Zachary P Wills,
Alan R Mardinly,
Linda Hu,
Paul L Greer,
Jay B Bikoff,
Hsin-Yi Henry Ho,
Michael J Soskis,
Mustafa Sahin and
Michael E Greenberg
Abstract
We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. The degradation of Ephexin5 promotes EphB-d...
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PMID: 21029865
PDF is available here.
Abstract
Epigenetic modifications of the genome are generally stable in somatic cells of multicellular organisms. In germ cells and early embryos, however, epigenetic reprogramming occurs on a genome-wide scale, which includes demethylation of DNA and remodeling of histones and their modifications. The mecha...
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PMID: 21030646
PDF is available here.
Abstract
We previously showed that neurotoxin-induced dopaminergic (DA) cell loss is decreased by inhibition of angiotensin receptors, but the location and functional effects of prorenin receptor (PRR) in the brain, including the DA system, are unknown. In the substantia nigra of Macaca fascicularis and in r...
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PMID: 20940627
PDF is available here.
Abstract
We identify in the mouse a subpopulation of the first (crescent-forming) field marked by endothelin receptor type A (Ednra) gene expression, which contributes to chamber myocardium through a unique type of cell behavior. Ednra-lacZ/EGFP-expressing cells arise in the ventrocaudal inflow region of the...
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PMID: 20929948
PDF is available here.
Abstract
We have identified and characterized MPP8 as a methyl-H3K9-binding protein. MPP8 displays an elevated expression pattern in various human carcinoma cells, whereas knocking-down MPP8 results in the loss of cellular mesenchymal marker as well as the reduction of tumour cell migration and invasiveness,...
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PMID: 20871592
PDF is available here.
Abstract
We show that the number of CREB-binding sites (CREs) affects whether the related histone acetyltransferases (HATs) CREB-binding protein (CBP) and p300 are required for endogenous gene transcription. Fibroblasts with both CBP and p300 knocked-out had strongly attenuated histone H4 acetylation at CREB...
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PMID: 20859256
PDF is available here.
Abstract
We observed that cholesterol abnormally accumulates in the endolysosomal membrane of LSD cells, thereby reducing the ability of lysosomes to efficiently fuse with endocytic and autophagic vesicles. Furthermore, we discovered that soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) re...
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PMID: 20871593
PDF is available here.
Abstract
We define the intracellular signaling events by which tissue plasminogen activator (tPA) promotes renal interstitial fibroblast proliferation. tPA promoted the proliferation of renal interstitial fibroblasts independent of its protease activity. The mitogenic effect of tPA required Tyr(4507) phospho...
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PMID: 20724593
PDF is available here.
Abstract
We have not only validated the role of PP2A in regulation of eIF4E phosphorylation but also demonstrated the mechanism underlying this process. Inhibition of PP2A using either okadaic acid or PP2A small interfering RNA (siRNA) increased eIF4E phosphorylation, which could be abolished by the presence...
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PMID: 20927323
PDF is available here.
Abstract
One of the biggest gaps in our knowledge about epigenomes is how their interplay with cellular signaling influences development, adult cellular differentiation and disease.
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PMID: 20944593
PDF is available here.
Abstract
A noninvasive imaging method for predicting how human embryos will develop may improve the success and safety of in vitro fertilization.
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PMID: 20944588
PDF is available here.
Abstract
Our results showed that stromal cells with the immunophenotypical (vimentin, CD34) and ultrastructural features of telocytes were present in the mouse heart since early embryonic to adult life, as well as in primary cultures of neonatal mouse cardiac cells. These cells formed an extended network of...
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PMID: 20977627
PDF is available here.
Sabine Jurado,
Ian Smyth,
Bryce van Denderen,
Nora Tenis,
Andrew Hammet,
Kimberly Hewitt,
Jane-Lee Ng,
Carolyn J McNees,
Sergei V Kozlov,
Hayato Oka,
Masahiko Kobayashi,
Lindus A Conlan,
Timothy J Cole,
Ken-Ichi Yamamoto,
Yoshihito Taniguchi,
Shunichi Takeda,
Martin F Lavin and
Jörg Heierhorst
Abstract
We show that absence of ASCIZ leads to p53-independent late-embryonic lethality in mice. Asciz-deficient primary fibroblasts exhibit increased sensitivity to DNA base damaging agents MMS and H2O2, but Asciz deletion knock-down does not affect ATM levels and activation in mouse, chicken, or human cel...
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PMID: 20975950
PDF is available here.