Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: Germany ; IN-VIVO ; SUPPORT ; GENE ; GENOME ; PROTEIN ; PROTEINS ; RNA ; TIME ; DNA ; FAMILY ; SUFFICIENT ; STAGE ; Drosophila ; MELANOGASTER ; DNA methylation ; EMBRYO ; FISSION YEAST ; METHYLTRANSFERASE ACTIVITY ; OVEREXPRESSION ; METHYLATION ; CATALYTIC ACTIVITY ; CYTOSINE-5 METHYLTRANSFERASES ; DE-NOVO METHYLATION ; DNA methylation,Drosophila,DNA methyltransferase,Dnmt2,Su(var)3-9 ; DNA methyltransferase ; EMBRYONIC STEM-CELLS ; EMBRYOS ; HISTONE H3 METHYLTRANSFERASE ; HYPERMETHYLATION ; LETHALITY ; MAMMALIAN DEVELOPMENT ; METHYLTRANSFERASE GENE ; SEQUENCE SPECIFICITY
    Abstract: The methylation status of Drosophila DNA has been discussed controversially over a long time. Recent evidence has provided strong support for the existence of 5-methylcytosine in DNA preparations from embryonic stages of fly development. The Drosophila genome contains a single candidate DNA methyltransferase gene that has been termed Dnmt2. This gene belongs to a widely conserved family of putative DNA methyltransferases. However, no catalytic activity has been demonstrated for any Dnmt2-like protein yet. We have now established a protocol for the immunological detection of methylated cytosine in fly embryos. Confocal analysis of immunostained embryos provided direct evidence for the methylation of embryonic DNA. In order to analyse the function of Dnmt2 in DNA methylation, we depleted the protein by RNA interference. Depletion of Dnmt2 had no detectable effect on embryonic development and resulted in a complete loss of DNA methylation. Consistently, overexpression of Dnmt2 from an inducible transgene resulted in significant genomic hypermethylation at CpT and CpA dinucleotides. These results demonstrate that Dnmt2 is both necessary and sufficient for DNA methylation in Drosophila and suggest a novel CpT/A-specific DNA methyltransferase activity for Dnmt2 proteins
    Type of Publication: Journal article published
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: ANGIOGENESIS ; EXPRESSION ; GROWTH ; SURVIVAL ; CELL ; ENDOTHELIAL GROWTH-FACTOR ; human ; IN-VIVO ; VIVO ; SUPPORT ; DEATH ; GENE ; COMPONENTS ; MOLECULES ; MICE ; recombination ; MOLECULE ; knockout ; MOUSE ; CELL-DEATH ; AGE ; MUTATION ; COMPONENT ; inactivation ; EXTRACELLULAR-MATRIX ; PHENOTYPE ; DEGRADATION ; RECRUITMENT ; BONE-FORMATION ; SKELETAL DEVELOPMENT ; HOMOLOGOUS RECOMBINATION ; LACKING ; MMP ; MATRIX ; DEFICIENCY ; PROGRAM ; VARIANT ; collagen ; MICE LACKING ; II COLLAGEN ; aggrecan ; chondrocyte ; collagenase ; COLLAGENASE CLEAVAGE SITE ; DEVELOPING LONG BONES ; hypertrophic cartilage ; HYPERTROPHIC CHONDROCYTES ; OSTEOARTHRITIC CARTILAGE ; PARATHYROID-HORMONE ; SPONDYLOEPIMETAPHYSEAL DYSPLASIA ; trabecular bone
    Abstract: The assembly and degradation of extracellular matrix (ECM) molecules are crucial processes during bone development. In this study, we show that ECM remodeling is a critical rate-limiting step in endochondral bone formation. Matrix metalloproteinase (MMP) 13 (collagenase 3) is poised to play a crucial role in bone formation and remodeling because of its expression both in terminal hypertrophic chondrocytes in the growth plate. p and in osteoblasts. Moreover, a mutation in the human MMP13 gene causes the Missouri variant of spondyloepimetaphyseal dysplasia. Inactivation of Mmp13 in mice through homologous recombination led to abnormal skeletal growth plate development. Chondrocytes differentiated normally but their exit from the growth plate was delayed. The severity of the Mmp13-null growth plate phenotype increased until about 5 weeks and completely resolved by 12 weeks of age. Mmp13-null mice had increased trabecular bone, which persisted for months. Conditional inactivation of Mmp13 in chondrocytes and osteoblasts showed that increases in trabecular bone occur independently of the improper cartilage ECM degradation caused by Mmp13 deficiency in late hypertrophic chondrocytes. Our studies identified the two major components of the cartilage ECM, collagen type II and aggrecan, as in vivo substrates for MMP13. We found that degradation of cartilage collagen and aggrecan is a coordinated process in which MMP13 works synergistically with MMP9. Mice lacking both MMP13 and MMP9 had severely impaired endochondral bone, characterized by diminished ECM remodeling, prolonged chondrocyte survival, delayed vascular recruitment and defective trabecular bone formation (resulting in drastically shortened bones). These data support the hypothesis that proper ECM remodeling is the dominant rate-limiting process for programmed cell death, angiogenesis and osteoblast recruitment during normal skeletal morphogenesis
    Type of Publication: Journal article published
    PubMed ID: 15539485
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: EXPRESSION ; SURVIVAL ; INHIBITION ; PATHWAY ; DIFFERENTIATION ; VESSELS ; REGRESSION ; BLOOD-BRAIN-BARRIER ; TNP-470 ; FUMAGILLIN
    Abstract: Multiple cell types involved in the regulation of angiogenesis express Wnt ligands. Although beta-catenin dependent and independent Wnt signaling pathways have been shown to control angiogenesis, the contribution of individual cell types to activate these downstream pathways in endothelial cells (ECs) during blood vessel formation is still elusive. To investigate the role of ECs in contributing Wnt ligands for regulation of blood vessel formation, we conditionally deleted the Wnt secretion factor Evi in mouse ECs (Evi-ECKO). Evi-ECKO mice showed decreased microvessel density during physiological and pathological angiogenesis in the postnatal retina and in tumors, respectively. The reduced microvessel density resulted from increased vessel regression accompanied by decreased EC survival and proliferation. Concomitantly, survival-related genes were downregulated and cell cycle arrest- and apoptosis-inducing genes were upregulated. EVI silencing in cultured HUVECs showed similar target gene regulation, supporting a mechanism of EC-derived Wnt ligands in controlling EC function. ECs preferentially expressed non-canonical Wnt ligands and canonical target gene expression was unaffected in Evi-ECKO mice. Furthermore, the reduced vascularization of Matrigel plugs in Evi-ECKO mice could be rescued by introduction of non-canonical Wnt5a. Treatment of mouse pups with the non-canonical Wnt inhibitor TNP470 resulted in increased vessel regression accompanied by decreased EC proliferation, thus mimicking the proliferation-dependent Evi-ECKO remodeling phenotype. Taken together, this study identified EC-derived non-canonical Wnt ligands as regulators of EC survival, proliferation and subsequent vascular pruning during developmental and pathological angiogenesis.
    Type of Publication: Journal article published
    PubMed ID: 24715464
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Abstract: The calcium ion regulates many aspects of neuronal migration, which is an indispensable process in the development of the nervous system. Calmodulin (CaM) is a multifunctional calcium ion sensor that transduces much of the signal. To better understand the role of Ca(2+)-CaM in neuronal migration, we investigated mouse precerebellar neurons (PCNs), which undergo stereotyped, long-distance migration to reach their final position in the developing hindbrain. In mammals, CaM is encoded by three non-allelic CaM (Calm) genes (Calm1, Calm2 and Calm3), which produce an identical protein with no amino acid substitutions. We found that these CaM genes are expressed in migrating PCNs. When the expression of CaM from this multigene family was inhibited by RNAi-mediated acute knockdown, inhibition of Calm1 but not the other two genes caused defective PCN migration. Many PCNs treated with Calm1 shRNA failed to complete their circumferential tangential migration and thus failed to reach their prospective target position. Those that did reach the target position failed to invade the depth of the hindbrain through the required radial migration. Overall, our results suggest the participation of CaM in both the tangential and radial migration of PCNs.
    Type of Publication: Journal article published
    PubMed ID: 25519244
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Abstract: Loss of TFAP2C in mouse leads to developmental defects in the extra-embryonic compartment with lethality at embryonic day (E)7.5. To investigate the requirement of TFAP2C in later placental development, deletion of TFAP2C was induced throughout extra-embryonic ectoderm at E6.5, leading to severe placental abnormalities caused by reduced trophoblast population and resulting in embryonic retardation by E8.5. Deletion of TFAP2C in TPBPA(+) progenitors at E8.5 results in growth arrest of the junctional zone. TFAP2C regulates its target genes Cdkn1a (previously p21) and Dusp6, which are involved in repression of MAPK signaling. Loss of TFAP2C reduces activation of ERK1/2 in the placenta. Downregulation of Akt1 and reduced activation of phosphorylated AKT in the mutant placenta are accompanied by impaired glycogen synthesis. Loss of TFAP2C led to upregulation of imprinted gene H19 and downregulation of Slc38a4 and Ascl2. The placental insufficiency post E16.5 causes fetal growth restriction, with 19% lighter mutant pups. Knockdown of TFAP2C in human trophoblast choriocarcinoma JAr cells inhibited MAPK and AKT signaling. Thus, we present a model where TFAP2C in trophoblasts controls proliferation by repressing Cdkn1a and activating the MAPK pathway, further supporting differentiation of glycogen cells by activating the AKT pathway.
    Type of Publication: Journal article published
    PubMed ID: 26811378
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    facet.materialart.
    Unknown
    Development 143 (17), 3045-3049 
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: PEPTIDE ; CELLS ; CELL ; human ; PATHWAY ; GENE ; GENES ; PROTEIN ; PROTEINS ; METABOLISM ; DIFFERENTIATION ; EPITHELIA ; MICE ; FAMILY ; MARKER ; animals ; KERATINOCYTES ; MOUSE ; HEALTH ; MUTATION ; genetics ; MARKERS ; PEPTIDES ; TRANSFORMATION ; PHENOTYPE ; REPRESSION ; epidermis ; REGULATOR ; WNT ; FOLLICLE ; signaling ; DEFICIENCY ; FAMILIES ; HAIR FOLLICLE ; hair ; CYSTEINE-RICH PROTEINS ; STRATIFIED EPITHELIA ; EPITHELIUM ; function ; STRATIFIED EPITHELIUM ; female ; Male ; FATE ; progenitor cell ; CHILD ; dkk ; biological markers ; growth & development ; Cornea ; embryology ; Gene Expression Regulation,Developmental ; Intercellular Signaling Peptides and Proteins ; Mice,Inbred C57BL ; Mice,Knockout
    Abstract: The Dkk family of secreted cysteine-rich proteins regulates Wnt/beta-catenin signaling by interacting with the Wnt co-receptor Lrp5/6. Here, we show that Dkk2-mediated repression of the Wnt/beta-catenin pathway is essential to promote differentiation of the corneal epithelial progenitor cells into a non-keratinizing stratified epithelium. Complete transformation of the corneal epithelium into a stratified epithelium that expresses epidermal-specific differentiation markers and develops appendages such as hair follicles is achieved in the absence of the Dkk2 gene function. We show that Dkk2 is a key regulator of the corneal versus epidermal fate of the ocular surface epithelium
    Type of Publication: Journal article published
    PubMed ID: 16672341
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    facet.materialart.
    Unknown
    Development 133 (), 4800-4801 
    Keywords: BIOLOGY ; developmental biology
    Type of Publication: Journal article published
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: brain ; RECEPTOR ; Germany ; IN-VIVO ; DIFFERENTIATION ; TISSUE ; MICE ; TISSUES ; TRANSGENIC MICE ; signaling ; CYTOKINE ; RE ; GLAND ; VIP ; DEVELOPMENTAL EXPRESSION ; neuron ; cholinergic ; CILIARY NEUROTROPHIC FACTOR ; IL6/IL-6 ; LEUKEMIA INHIBITORY FACTOR ; PEPTIDERGIC PROPERTIES ; PLASTICITY INVIVO ; RAT SWEAT GLANDS ; RECEPTOR-ALPHA-COMPONENT ; SECRETORY RESPONSIVENESS ; sympathetic ; VAChT ; VESICULAR ACETYLCHOLINE TRANSPORTER
    Abstract: Sympathetic neurons are generated through a succession of differentiation steps that initially lead to noradrenergic neurons innervating different peripheral target tissues. Specific targets, like sweat glands in rodent footpads, induce a change from noradrenergic to cholinergic transmitter phenotype. Here, we show that cytokines acting through the gp130 receptor are present in sweat glands. Selective elimination of the gp130 receptor in sympathetic neurons prevents the acquisition of cholinergic and peptidergic features (VAChT, ChT1, VIP) without affecting other properties of sweat gland innervation. The vast majority of cholinergic neurons in the stellate ganglion, generated postnatally, are absent in gp130-deficient mice. These results demonstrate an essential role of gp130-signaling in the target-dependent specification of the cholinergic neurotransmitter phenotype
    Type of Publication: Journal article published
    PubMed ID: 16319110
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: GROWTH ; Germany ; INFORMATION ; SYSTEM ; MECHANISM ; EVOLUTION ; SPEMANN ORGANIZER ; WNT ; signaling ; BMP ; development ; NEURAL INDUCTION ; WNT/BETA-CATENIN ; MORPHOGEN GRADIENT ; XENOPUS-EMBRYOS ; morphogen ; Amphioxus ; ANIMAL-VEGETAL AXIS ; CIRRIPEDE CRUSTACEAN ; Echinoderms ; Embryonic axis ; FITNESS CONSEQUENCES ; NUCLEAR BETA-CATENIN ; Planaria ; PLANARIAN REGENERATION ; SEA-URCHIN EMBRYO ; Size scaling ; Urbilateria
    Abstract: The regulation of body axis specification in the common ancestor of bilaterians remains controversial. BMP signaling appears to be an ancient program for patterning the secondary, or dorsoventral, body axis, but any such program for the primary, or anteroposterior, body axis is debated. Recent work in invertebrates indicates that posterior Wnt/beta-catenin signaling is such a mechanism and that it evolutionarily predates the cnidarian-bilaterian split. Here, I argue that a Cartesian coordinate system of positional information set up by gradients of perpendicular Wnt and BMP signaling is conserved in bilaterians, orchestrates body axis patterning and contributes to both the relative invariance and diversity of body forms
    Type of Publication: Journal article published
    PubMed ID: 20179091
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...