- Developmental Biology and Gene Regulation
- Genomics and Chromatin Dynamics
- Congenital heart defects research
- Hedgehog Signaling Pathway Studies
- Congenital limb and hand anomalies
- Animal Genetics and Reproduction
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Molecular Biology Techniques and Applications
- Fibroblast Growth Factor Research
- Renal and related cancers
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- dental development and anomalies
- Reproductive Biology and Fertility
- Muscle Physiology and Disorders
- Hippo pathway signaling and YAP/TAZ
- RNA modifications and cancer
- TGF-β signaling in diseases
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Cellular Mechanics and Interactions
- Urological Disorders and Treatments
- Cell Image Analysis Techniques
- Mesenchymal stem cell research
- 3D Printing in Biomedical Research
University of Basel
2014-2025
Freiwillige Akademische Gesellschaft
2015
École Polytechnique Fédérale de Lausanne
2009
SIB Swiss Institute of Bioinformatics
2009
Texas A&M Health Science Center
2009
Institut de Biologie du Développement Marseille
2005
Utrecht University
1999-2004
European Molecular Biology Laboratory
1989-2003
Heidelberg University
2003
Albert Einstein College of Medicine
2003
INTRODUCTION Hematoxylin and eosin (H&E) stains have been used for at least a century are still essential recognizing various tissue types the morphologic changes that form basis of contemporary cancer diagnosis. The stain has unchanged many years because it works well with variety fixatives displays broad range cytoplasmic, nuclear, extracellular matrix features. deep blue-purple color nucleic acids by complex, incompletely understood reaction. Eosin is pink proteins nonspecifically. In...
Mesenchymal stem/stromal cells (MSC) are typically used to generate bone tissue by a process resembling intramembranous ossification, i.e., direct osteoblastic differentiation. However, most bones develop endochondral via remodeling of hypertrophic cartilaginous templates. To date, formation has not been reproduced using human, clinically compliant cell sources. Here, we aimed at engineering tissues from marrow-derived, adult human MSC with an intrinsic capacity undergo ossification. By...
Distal limb development and specification of digit identities in tetrapods are under the control a mesenchymal organizer called polarizing region. Sonic Hedgehog (SHH) is morphogenetic signal produced by region posterior bud. Ectopic anterior SHH signaling induces duplications has been suspected as major cause underlying congenital malformations that result polydactyly. Here, we report polydactyly Gli3-deficient mice arises independently signaling. Disruption one or both Gli3 alleles mouse...
Epithelial-mesenchymal feedback signaling is the key to diverse organogenetic processes such as limb bud development and branching morphogenesis in kidney lung rudiments. This study establishes that BMP antagonist gremlin (Grem1) essential initiate these epithelial-mesenchymal interactions during metanephric organogenesis. A Grem1 null mutation mouse generated by gene targeting causes neonatal lethality because of lack kidneys septation defects. In early buds, mesenchymal required establish...
The polarization of nascent embryonic fields and the endowment cells with organizer properties are key to initiation vertebrate organogenesis. One such event is antero-posterior (AP) early limb buds activation morphogenetic Sonic Hedgehog (SHH) signaling in posterior mesenchyme, which turn promotes outgrowth specifies pentadactylous autopod. Inactivation Hand2 transcriptional regulator from onset mouse forelimb bud development disrupts establishment identity Shh expression, results a...
The spine apparatus is a cellular organelle that present in many dendritic spines of excitatory neurons the mammalian forebrain. Despite its discovery >40 years ago, function still unknown although calcium buffering functions as well roles synaptic plasticity have been proposed. We recently shown 100-kDa protein synaptopodin associated with apparatus. Here, we now report mice homozygous for targeted deletion gene completely lack apparatuses. Interestingly, this absence accompanied by...
The bHLH transcription factor dHAND is required for establishment of SHH signaling by the limb bud organizer in posterior mesenchyme, a step crucial to development vertebrate paired appendages. We show that transcriptional repressor GLI3 restricts expression mesenchyme prior activation mouse buds. dHAND, turn, excludes anterior genes such as Gli3 and Alx4 from mesenchyme. Furthermore, genetic interaction directs SHH/FGF feedback loop restricting BMP antagonist GREMLIN posteriorly. These...
Expression of the gene encoding atrial natriuretic factor (ANF) during mouse cardiac embryogenesis was studied using in situ hybridization to histologic sections. ANF mRNA first detected a subpopulation myocardial cells at day 8 embryogenesis. During 9, abundant probe atrium and primitive ventricle found. At 14, strong labeling both atria trabeculated regions left seen, whereas fewer right expressed gene. The developmental regulation expression ventricular suggests an important role for this...
In an effort to identify widely active positive regulatory elements, we have examined the action of cytomegalovirus enhancer-promoter in transgenic mice. These elements activated expression 24 28 tissues tested. The greatest was observed heart, kidney, brain, and testis. Maximum further localized specific cells within heart kidney.
Antagonists act to restrict and negatively modulate the activity of secreted signals during progression embryogenesis. In mouse embryos lacking extra-cellular BMP antagonist gremlin 1 (Grem1), metanephric development is disrupted at stage initiating ureteric bud outgrowth. Treatment mutant kidney rudiments in culture with recombinant protein induces additional epithelial buds restores outgrowth branching. All express Wnt11, Gdnf significantly upregulated surrounding mesenchyme, indicating...
Embryogenesis depends on self-regulatory interactions between spatially separated signaling centers, but few of these are well understood. Limb development is regulated by epithelial-mesenchymal (e-m) feedback loops sonic hedgehog (SHH) and fibroblast growth factor (FGF) involving the bone morphogenetic protein (BMP) antagonist Gremlin1 (GREM1). By combining mouse molecular genetics with mathematical modeling, we showed that BMP4 first initiates SHH then propagates e-m through differential...
Pigmented lesions involving ocular structures are always a source of concern until proved benign. We wish to call attention striking pigment change, the eye and eyelids, which is benign but simulates malignant disease. Because there exists confusion names describing pigmentary abnormalities surrounding structures, new terminology suggested. These terms describe presence of<i>ectopic</i>melanin-forming cells (melanocytes) in unusual sites number skin eye. The following Tabulation summarizes...
The mouse limb deformity ( ld ) mutations cause malformations by disrupting epithelial–mesenchymal signaling between the polarizing region and apical ectodermal ridge. Formin was proposed as relevant gene because three of five alleles disrupt its C-terminal domain. In contrast, our studies establish that two other directly neighboring Gremlin gene, corroborating requirement this BMP antagonist for morphogenesis. Further doubts concerning an involvement in phenotype are cast, a targeted...
The essential roles of SHH in anteroposterior (AP) and AER-FGF signalling proximodistal (PD) limb bud development are well understood. In addition, these morphoregulatory signals key components the self-regulatory SHH/GREM1/AER-FGF feedback system that regulates distal progression development. This study uncovers an additional module required for coordinated axis Transcriptome analysis using Shh-deficient mouse buds revealed expression proximal genes was distally extended from early stages...