Lieven Gevaert

Lieven Gevaert
GENTAUR Institute BVBA · Research

About

106
Publications
15,629
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
6,252
Citations
Introduction
Born in Gent, highschool Instituut van Gent, FLTBW Bio-engineering Biotechnology, internships at INRA, ENSAM, INSERM, CEMAGREF and CIRAD Montpellier. Work in Brussels, Aachen, Paris, Eindhoven, London, Gdansk, Sofia and San Francisco. Give product advice at KULeuven, ULB, UCL, FUNDP, RUG, UIA, UA, ULG, Institut Pasteur Lille et Paris, GSK, Johnson Johnson Beerse, ERASMUS univeristeit Rotterdam, Universiteit Leiden, AMC, Institut Cochin, BioMeriux, Loreal, BASF
Additional affiliations
January 2011 - present
January 2008 - December 2009
Washington University in St. Louis
January 2008 - present
Flanders Institute for Biotechnology
Education
August 1989 - July 1996
RUG FLTBW
Field of study
  • Biotechnology

Publications

Publications (106)
Article
Anemia suppresses liver hepcidin expression to supply adequate iron for erythropoiesis. Erythroferrone mediates hepcidin suppression by anemia, but its mechanism of action remains uncertain. The bone morphogenetic protein (BMP)-SMAD signaling pathway has a central role in hepcidin transcriptional regulation. Here, we explored the contribution of in...
Article
Full-text available
In human ESCs the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out tem...
Article
Full-text available
Thyroid follicles, the functional units of the thyroid gland, are delineated by a monolayer of thyrocytes resting on a continuous basement membrane. The developmental mechanisms of folliculogenesis, whereby follicles are formed by the reorganization of a non-structured mass of non-polarized epithelial cells, are largely unknown. Here we show that a...
Article
Full-text available
Naive mouse embryonic stem cells (mESCs) are in a metastable state and fluctuate between inner cell mass- and epiblast-like phenotypes. Here, we show transient activation of the BMP-SMAD signaling pathway in mESCs containing a BMP-SMAD responsive reporter transgene. Activation of the BMP-SMAD reporter transgene in naive mESCs correlated with lower...
Data
Table S1. Differentially Expressed Genes between GFP++ and GFP− BRE:gfp mESCs and between S1fl/flS5fl/fl and S1−/−S5−/− mESCs
Data
Table S2. Differential DNA Methylation between GFP++ and GFP− BRE:gfp mESCs and between S1fl/flS5fl/fl and S1−/−S5−/− mESCs
Data
Table S3. Counts of SMAD Binding Motifs GGCGCC/GCCG in the Promoters of Differentially Expressed Genes between S1fl/flS5fl/fl and S1−/−S5−/− mESCs
Article
Full-text available
Mesoangioblasts (MABs) are vessel-associated stem cells that express pericyte marker genes and participate in skeletal muscle regeneration. Molecular circuits that regulate the myogenic commitment of MABs are still poorly characterized. The critical role of bone morphogenetic protein (BMP) signalling during proliferation and differentiation of adul...
Article
Full-text available
Collateral remodeling is critical for blood flow restoration in peripheral arterial disease and is triggered by increasing fluid shear stress in preexisting collateral arteries. So far, no arterial-specific mediators of this mechanotransduction response have been identified. We show that muscle segment homeobox 1 (MSX1) acts exclusively in collater...
Article
To investigate the necessity of the canonical BMP pathway during osteoclast differentiation, we created osteoclasts with a conditional gene deletion for Smad1 and Smad5 (SMAD1/5), or Smad4 using adenovirus expressing CRE recombinase (Ad-CRE). Reduction of either Smad4 or Smad1/5 expression resulted in fewer and smaller multinuclear cells compared t...
Article
Full-text available
[This corrects the article , PMID: 22966238.].
Data
Myeloid cells are not significantly affected by etoposide treatment. FACS analysis of Mac1+ myeloid cells in bone marrow in wild-type and Tdp2Δ1–3 animals 6 days after treatment with 75 mg/kg etoposide or vehicle control (DMSO). Scatter plot (A) and quantification (B) are shown. The mild increase correlates with the observed decrease in lymphocite...
Data
Cell cycle dependent induction of DSBs following etoposide treatment in primary MEFs. DSBs detected as γH2AX foci (bottom left), Cyclin A content (Cyc A, top right), 5-ethynyl-2′-deoxyuridine incorporation (EdU, bottom right) and DAPI counterstain (top left) are shown. G1 (Cyc A negative, EdU negative), S-phase (Cyc A positive, EdU positive) and G2...
Data
The absence of TDP2 sensitizes lymphocyte precursors to etoposide treatment in vivo. FACS analysis of B-cells in bone marrow (A) and T-cells in thymus (B) in wild-type and Tdp2Δ1–3 animals 6 days after treatment with 75 mg/kg etoposide or vehicle control (DMSO). Pro-B cell (CD43+ B220+), Pre-B cell (CD43− B220low) immature B cell (CD43− B220high) a...
Data
TDP2 depletion impairs repair of TOP2-induced DSBs in human A549 cells. A. γH2AX foci induction after 30 min 50 µM etoposide treatment and repair at different times following drug removal in G1 TDP2-depleted (pS-TDP2) and control non-depleted (pS) cells. B. G2 cells with 10 µM etoposide treatment. Other details as in “A”. Average ± s.e.m. of at lea...
Data
TDP2 promotes survival following TOP2-induced DSBs in mammalian cells. Clonogenic survival of wild-type and Tdp2Δ1–3 transformed MEFs after continuous exposure to the indicated concentrations of etoposide. Average ± s.e.m. of three independent experiments and statistical significance by Two-way ANOVA test with Bonferroni post-test is shown. (TIF)
Data
Targeted deletion of KU70 in DT40 cells. Southern-blot analysis of EcoRI-digested DNA from wild-type (+/+), heterozygous (+/−) and knock-out (−/−) DT40 cells in TDP2+/+/+ and TDP2−/−/− background. A probe hybridizing to a region of the KU70 locus not contained in the deletion construct was used. The 5.5-kb (wild-type) and 2.8-kb (deleted) expected...
Article
Full-text available
Anticancer topoisomerase "poisons" exploit the break-and-rejoining mechanism of topoisomerase II (TOP2) to generate TOP2-linked DNA double-strand breaks (DSBs). This characteristic underlies the clinical efficacy of TOP2 poisons, but is also implicated in chromosomal translocations and genome instability associated with secondary, treatment-related...
Article
Vascular patterning involves sprouting of blood vessels, which is governed by orchestrated communication between cells in the surrounding tissue and endothelial cells (ECs) lining the blood vessels. Single ECs are selected for sprouting by hypoxia-induced stimuli and become the 'tip' or leader cell that guides new sprouts. The 'stalk' or trailing E...
Article
Full-text available
The strength and spatiotemporal activity of Nodal signaling is tightly controlled in early implantation mouse embryos, including by autoregulation and feedback loops, and involves secreted and intracellular antagonists. These control mechanisms, which are established at the extra-embryonic/embryonic interfaces, are essential for anterior-posterior...
Article
Full-text available
Tracing the precise developmental origin of amnion and amnion-derived stem cells is still challenging and depends chiefly on analyzing powerful genetic model amniotes like mouse. Profound understanding of the fundamental differences in amnion development in both the disc-shaped primate and human embryo and the cup-shaped mouse embryo is pivotal in...
Article
Full-text available
The abortive activity of topoisomerases can result in clastogenic and/or lethal DNA damage in which the topoisomerase is covalently linked to the 3'- or 5'-terminus of a DNA strand break. This type of DNA damage is implicated in chromosome translocations and neurological disease and underlies the clinical efficacy of an important class of anticance...
Article
Gradients of vascular endothelial growth factor (VEGF) induce single endothelial cells to become leading tip cells of emerging angiogenic sprouts. Tip cells then suppress tip-cell features in adjacent stalk cells via Dll4/Notch-mediated lateral inhibition. We report here that Smad1/Smad5-mediated BMP signaling synergizes with Notch signaling during...
Article
Signaling by the many ligands of the TGFβ family strongly converges towards only five receptor-activated, intracellular Smad proteins, which fall into two classes i.e. Smad2/3 and Smad1/5/8, respectively. These Smads bind to a surprisingly high number of Smad-interacting proteins (SIPs), many of which are transcription factors (TFs) that co-operate...
Article
We performed a genotoxicity investigation of extremely low-frequency (ELF) magnetic fields (MFs, 50 Hz, 100 and 500 µT, 1 and 2 h exposure) alone and in combination with known chemical mutagens using the VITOTOX test. This test is a very sensitive reporter assay of Salmonella typhimurium bacteria based on the SOS response. Our study showed that ELF...
Article
Full-text available
We investigated the genotoxic properties of a number of extracts from Tunisian traditional medicinal plants with the bacterial VITOTOX test in Salmonella typhimurium and the alkaline comet assay in human C3A cells. Ethyl acetate and methanol extracts from Marrubium alysson L. and Retama raetam (Forsk.) Webb and methanol extracts from Peganum harmal...
Article
Full-text available
The regulation of intestinal epithelial cell adhesion and migratory properties is often compromised in inflammatory bowel disease (IBD). Despite an increasing interest in bone morphogenetic protein (Bmp) signaling in gut pathologies, little is known of the specific roles played by individual Smads in intestinal epithelial functions. In the present...
Article
Full-text available
The genotoxicity and toxicity of ethnomedicinal Philippine plants, which include Cassia fistula, Derris elliptica, Ficus elastica, Gliciridia sepium, Michelia alba, Morus alba, Pogostemon cablin and Ricinus communis, were tested using the Vitotox assay. The plants are used traditionally to treat several disorders like diabetes, weakness, menorrhagi...
Article
Bone morphogenetic protein 4 (Bmp4) is essential for lung development. To define the intracellular signaling mechanisms by which Bmp4 regulates lung development, BMP-specific Smad1 or Smad5 was selectively knocked out in fetal mouse lung epithelial cells. Abrogation of lung epithelial-specific Smad1, but not Smad5, resulted in retardation of lung b...
Article
Full-text available
Zeb2 (Sip1/Zfhx1b) is a member of the zinc-finger E-box-binding (ZEB) family of transcriptional repressors previously demonstrated to regulate epithelial-to-mesenchymal transition (EMT) processes during embryogenesis and tumor progression. We found high Zeb2 mRNA expression levels in HSCs and hematopoietic progenitor cells (HPCs), and examined Zeb2...
Article
Smoke, smoke-water and aerosols have a stimulatory effect on seed germination and growth vigour of many seedlings, making them potentially useful for different purposes, provided they do not pose a health risk. Therefore, the genotoxicity of two kinds of smoke-water and 3,7-dimethyl-2H-furo[2,3-c]pyran-2-one, a variant of the most active smoke comp...
Article
Ligands of the Transforming Growth Factor type beta (TGFbeta) family exert multiple and sometimes opposite effects on most cell types in vivo depending on cellular context, which mainly includes the stage of the target cell, the local environment of this cell or niche, and the identity and the dosage of the ligand. Significant progress has been mad...
Article
BMPs play multiple roles in development and BMP signaling is essential for lens formation. However, the mechanisms by which BMP receptors function in vertebrate development are incompletely understood. To determine the downstream effectors of BMP signaling and their functions in the ectoderm that will form the lens, we deleted the genes encoding th...
Article
There are conflicting reports about whether BMP signaling is required for eyelid closure during fetal development. This question was addressed using mice deficient in BMP or TGFbeta signaling in prospective eyelid and conjunctival epithelial cells. Genes encoding two type I BMP receptors, the type II TGFbeta receptor, two BMP- or two TGFbeta-activa...
Article
Full-text available
Deposition of the amyloid-β peptide is a pathological hallmark of Alzheimer's disease. A high-throughput functional genomics screen identified G protein–coupled receptor 3 (GPR3), a constitutively active orphan G protein–coupled receptor, as a modulator of amyloid-β production. Overexpression of GPR3 stimulated amyloid-β production, whereas genetic...
Article
Full-text available
Gene trapping in mouse embryonic stem (ES) cells enables near-saturation vector-based insertional mutagenesis across the genome of this model organism. About 135,000 trapped ES cell lines are made available to the scientific community by the International Gene Trap Consortium (IGTC; www.genetrap.org). A search of one of its databases identified an...
Article
With every heartbeat the heart must contract and relax. This seemingly trivial process critically needs tight control of contraction and relaxation phases, and extremely efficient coordination between these two phases to control blood flow and maintain cardiac homeostasis. To achieve this, specialized sensors are required to detect the inherent rep...
Article
Full-text available
Bone morphogenetic protein (BMP) signaling is essential for the induction and subsequent development of the lens. The purpose of this study was to analyze the function(s) of the type 1 BMP receptor, Acvr1, in lens development. Acvr1 was deleted from the surface ectoderm of mouse embryos on embryonic day 9 using the Cre-loxP METHOD: Cell proliferati...
Chapter
The last decade has witnessed a quantum leap in our technical abilities to generate transgenic mice, up to the point that transgenic mouse models for any aspect of normal and pathologic physiology are within reach. Most difficult to attain, and impossible in humans, are invasive approaches in vivo, to define the molecular, biochemical and cellular...
Article
Full-text available
The transforming growth factor β (TGFβ) family has critical roles in the regulation of fertility. In addition, the pathogenesis of some human cancers is attributed to misregulation of TGFβ function and SMAD2 or SMAD4 mutations. There are limited mouse models for the BMP signaling SMADs (BR-SMADs) 1, 5, and 8 because of embryonic lethality and suspe...
Article
Smads are intracellular signaling proteins that transduce signals elicited by members of the transforming growth factor (TGF)-beta superfamily. Smad5 and Smad1 are highly homologous, and they mediate primarily bone morphogenetic protein (Bmp) signals. We used the Cre-loxP system and Sm22-Cre and Tie-1-Cre mice to study the function of Smad5 in the...
Article
Full-text available
Smad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early proge...
Article
A complex mutation in DFNA5, resulting in exon 8 skipping, causes autosomal dominant hearing impairment, which starts in the high frequencies between 5 and 15 years of age and progressively affects all frequencies. To study its function in vivo, Dfna5 knockout mice were generated through the deletion of exon 8, simultaneously mimicking the human mu...
Article
Full-text available
We investigated whether peroxisome proliferator-activated receptor gamma (PPARgamma) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. Inducing expression or activating PPARgamma using synthetic agonists of the thiazolinedione family results in a dramatic decrease in the levels of the amyloid-beta (Abeta) pepti...
Article
Full-text available
Presenilin 1 (PS1) interacts with telencephalin (TLN) and the amyloid precursor protein via their transmembrane domain (Annaert, W.G., C. Esselens, V. Baert, C. Boeve, G. Snellings, P. Cupers, K. Craessaerts, and B. De Strooper. 2001. Neuron. 32:579-589). Here, we demonstrate that TLN is not a substrate for gamma-secretase cleavage, but displays a...
Article
Full-text available
The Presenilins are part of the gamma-secretase complex that is involved in the regulated intramembrane proteolysis of amyloid precursor protein and other type I integral membrane proteins. Nicastrin, Pen-2, and Aph1 are the other proteins of this complex. The Presenilins probably contribute the catalytic activity to the protease complex. However,...
Article
Smad5 is a member of the Smad family of intracellular mediators of BMP signals and in endothelial cells of TGF-beta signals. We and others previously showed that loss of Smad5 in the mouse results in embryonic lethality (between E9.5-E11.5) due to multiple embryonic and extraembryonic defects. To circumvent the early embryonic lethality and to allo...
Article
Full-text available
The metalloprotease ADAM 10 is an important APP alpha-secretase candidate, but in vivo proof of this is lacking. Furthermore, invertebrate models point towards a key role of the ADAM 10 orthologues Kuzbanian and sup-17 in Notch signalling. In the mouse, this function is, however, currently attributed to ADAM 17/TACE, while the role of ADAM 10 remai...
Article
Full-text available
In the brain of Alzheimer's disease (AD) patients, neurotoxic amyloid peptides accumulate and are deposited as senile plaques. A major therapeutic strategy aims to decrease production of amyloid peptides by inhibition of gamma-secretase. Presenilins are polytopic transmembrane proteins that are essential for gamma-secretase activity during developm...
Article
One of the landmarks of Alzheimer's disease are neurofibrillary tangles (NFT) in the brain. NFT mainly consist of a hyperphosphorylated form of the protein tau, which is responsible for stabilisation of the neuronal cytoskeleton by microtubule binding and is unable to function properly in its hyperphosphorylated form. Glycogen synthase kinase-3beta...
Article
The identification and characterization of components of the transforming growth factor β (TGFβ) signalling pathway are proceeding at a very fast pace. To illustrate a number of our activities in this field, we first summarize our work aiming at the selection from a large collection of single residue substitution mutants of two activin A polypeptid...
Article
Biochemical and structural analysis of the phosphorylation sites of human protein tau of paired helical filaments in the brain of Alzheimer's disease patients revealed that many sites consist of serine or threonine residues followed by a proline residue. In the brain of Alzheimer's disease patients, NFT were demonstrated to be immunoreactive for gl...
Article
Full-text available
Protein tau filaments in brain of patients suffering from Alzheimer's disease, frontotemporal dementia, and other tauopathies consist of protein tau that is hyperphosphorylated. The responsible kinases operating in vivo in neurons still need to be identified. Here we demonstrate that glycogen synthase kinase-3β (GSK-3β) is an effective kinase for p...
Article
Deposition of amyloid β-peptide (Aβ) in cerebral vessel walls (cerebral amyloid angiopathy, CAA) is very frequent in Alzheimer’s disease and occurs also as a sporadic disorder. Here, we describe significant CAA in addition to amyloid plaques, in aging APP/Ld transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP) e...