A5082056949- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- Adipose Tissue and Metabolism
- dental development and anomalies
- Receptor Mechanisms and Signaling
- Developmental Biology and Gene Regulation
- Osteoarthritis Treatment and Mechanisms
- Diet and metabolism studies
- Ubiquitin and proteasome pathways
- Cancer Cells and Metastasis
- Neuropeptides and Animal Physiology
- Hedgehog Signaling Pathway Studies
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Connective tissue disorders research
- Genetics and Neurodevelopmental Disorders
- Single-cell and spatial transcriptomics
- Nasal Surgery and Airway Studies
- Bone and Dental Protein Studies
- Pancreatic function and diabetes
- Birth, Development, and Health
- Marine and fisheries research
- Sustainable Agricultural Systems Analysis
- Congenital Ear and Nasal Anomalies
- Bone Metabolism and Diseases
Leipzig University
2021-2025
University Medical Center
2025
Karolinska Institutet
2013-2023
University Hospital Leipzig
2023
Medical University of Vienna
2016-2022
University Medical Center Hamburg-Eppendorf
2020-2021
Universität Hamburg
2020-2021
Neurosciences Institute
2018
University of California, San Diego
2016
University of Bonn
2016
Neural crest cells are embryonic progenitors that generate numerous cell types in vertebrates. With single-cell analysis, we show mouse trunk neural become biased toward neuronal lineages when they delaminate from the tube, whereas cranial acquire ectomesenchyme potential dependent on activation of transcription factor Twist1. The choices make to sensory, glial, autonomic, or mesenchymal can be formalized as a series sequential binary decisions. Each branch decision tree involves initial...
Following the yellow brick road The adrenal glands affect a variety of processes such as stress responses and metabolism. mature gland is formed from multiple tissue sources, including cells neural origin. Furlan et al. traced origins these cells. first become Schwann cell precursors follow along nerves to travel dorsal root ganglia spine gland. Once there, differentiate into chromaffin authors used singlecell transcriptomics reveal shifts in functional programs during migration,...
Abstract Ribosome biogenesis is a canonical hallmark of cell growth and proliferation. Here we show that execution Epithelial-to-Mesenchymal Transition (EMT), migratory cellular program associated with development tumor metastasis, fueled by upregulation ribosome during G1/S arrest. This unexpected EMT feature independent species initiating signal, accompanied release the repressive nucleolar chromatin remodeling complex (NoRC) from rDNA, together recruitment EMT-driving transcription factor...
Abstract Understanding cell types and mechanisms of dental growth is essential for reconstruction engineering teeth. Therefore, we investigated cellular composition growing non-growing mouse human As a result, report an unappreciated complexity the continuously-growing incisor, which suggests coherent model dynamics enabling unarrested growth. This relies on spatially-restricted stem, progenitor differentiated populations in epithelial mesenchymal compartments underlying coordinated...
Abstract Class F receptors are considered valuable therapeutic targets due to their role in human disease, but structural changes accompanying receptor activation remain unexplored. Employing population and cancer genomics data, analyses, molecular dynamics simulations, resonance energy transfer-based approaches mutagenesis, we identify a conserved basic amino acid TM6 that acts as switch mediate activation. Across all tested (FZD 4,5,6,7, SMO), mutation of the confers an increased potency...
Facial shaping results from oriented divisions and crowd movements of ectomesenchymal cells during morphogenetic events.
Abstract G protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors. They can exist and act as dimers, but requirement dimers for agonist-induced signal initiation structural dynamics remains largely unknown. Frizzled 6 (FZD ) is a member Class F GPCRs, which bind WNT proteins to initiate signaling. Here, we show that FZD dimerizes dimer interface formed by transmembrane α-helices four five. Most importantly, present dissociation/re-association GPCR through...
Frizzleds (FZDs) are classified as G-protein-coupling receptors, but how signals initiated and specified through heterotrimeric G proteins is unknown. FZD6 regulates convergent extension movements, its C-terminal Arg511Cys mutation causes nail dysplasia in humans. We investigated the functional relationship between FZD6, Disheveled (DVL), proteins. Live cell imaging combined with fluorescence recovery after photobleaching (FRAP) revealed that inactive human precouples to Gαi1 Gαq not...
Abstract WNT-Frizzled (FZD) signaling plays a critical role in embryonic development, stem cell regulation and tissue homeostasis. FZDs are linked to severe human pathology seen as promising target for therapy. Despite intense efforts, no small molecule drugs with distinct efficacy have emerged. Here, we identify the Smoothened agonist SAG1.3 partial of FZD 6 limited subtype selectivity. Employing extensive silico analysis, resonance energy transfer- luciferase-based assays describe mode...
Cartilaginous structures are at the core of embryo growth and shaping before bone forms. Here we report a novel principle vertebrate cartilage that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism uncouples lateral expansion curved cartilaginous sheets from control thickness, process which might be evolutionary underlying adaptations facial shape. In rod-shaped (Meckel, ribs skeletal elements in developing limbs), transverse integration clonal...
Facial shape is the basis for facial recognition and categorization. features reflect underlying geometry of skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw face) shaped by signals generated neural structures: brain olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables induction septum posterior capsule, whereas formation a roof controlled from Unexpectedly, cartilage turned out be important shaping membranous bones during...
Reef-building corals are endangered animals with a complex colonial organization. Physiological mechanisms connecting multiple polyps and integrating them into coral colony still enigmatic. Using live imaging, particle tracking, mathematical modeling, we reveal how connect individual form integrated polyp groups via species-specific, complex, stable networks of currents at their surface. These involve surface mucus different concentrations, which regulate joint feeding the colony. Inside...
Frizzleds (FZDs) are unconventional G protein–coupled receptors that belong to the class Frizzled. They bound and activated by Wingless/Int-1 lipoglycoprotein (WNT) family of secreted lipoglycoproteins. To date, mechanisms signal initiation FZD–G protein coupling remain poorly understood. Previously, we showed FZD<sub>6</sub> assembles with G<i>α</i><sub>i1</sub>/G<i>α</i><sub>q</sub> (but not G<i>α</i><sub>s</sub>, G<i>α</i><sub>o</sub> Ga<sub>12/13</sub>), these inactive-state complexes...
Abstract Objectives This study aims to investigate the impact of pro-osteoblastogenic ERK-activated ribosomal S6 kinase ( Rsk2) on Tumor necrosis factor (TNF)α-induced bone loss in craniofacial system, focusing its role rheumatoid arthritis (RA). The objective is understand whether Rsk2 , previously shown have protective effects long bones against TNFα-induced resorption, exhibits similar region. Materials and Methods. compares mice with TNFα overexpression, knockout mice, a combination...
Mechanosensory ion channels are proteins that sensitive to mechanical forces. They found in tissues throughout the body and play an important role bone remodeling by sensing changes stress transmitting signals bone-forming cells. Orthodontic tooth movement (OTM) is a prime example of mechanically induced remodeling. However, cell-specific Piezo1 Piezo2 OTM has not been investigated yet. Here we first identify expression PIEZO1/2 dentoalveolar hard tissues. Results showed PIEZO1 was expressed...
The tight link between brain and skull formation is a fundamental aspect of vertebrate evolution embryogenesis. Their developmental synchronization essential for structural functional integration. shape coevolution evident along the phylogeny; however, genetic basis underlying their close evolutionary relationship remains little explored. Here, we reveal function MN1 gene that was previously found to be associated with significant variation in mouse cranial bones. We show evolved from an...
The capacity of a tissue to continuously alter its phenotype lies at the heart how an animal is able quickly adapt changes in environmental stimuli. Within tissues, differentiated cells are rigid and play limited role adapting new environments; however, replenished by stem that defined their phenotypic plasticity. Here we demonstrate Wnt-responsive cell niche junctional epithelium responsible for capability this physical consistency diet. Mechanical input from chewing required both establish...
The WNT/planar-cell-polarity (PCP) pathway is a key regulator of cell polarity and directional movements. Core PCP proteins such as Van Gogh-like2 (VANGL2) are evolutionarily highly conserved; however, the mammalian machinery still poorly understood mainly due to lack suitable models quantitative methodology. WNT/PCP has been implicated in many human diseases with most distinguished positive role metastatic process, which accounts for more than 90% cancer related deaths, presents therefore...
Mineralized tissues, such as bones or teeth, are essential structures of all vertebrates. They enable rapid movement, protection, and food processing, in addition to providing physiological functions. Although the development, regeneration, pathogenesis teeth have been intensely studied, there is currently no tool accurately follow dynamics growth healing these vital tissues space time. Here, we present BEE-ST (Bones tEEth Spatio-Temporal monitoring) approach, which allows precise...
Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in nervous system their affinities to neurotransmitter reuptake vesicular transporters heighten availability extracellularly. Exacerbated dopamine particularly considered as key determinant of...
Abstract There are major differences in duration and scale at which limb development regeneration proceed, raising the question to what extent is a recapitulation of development. We address this by analyzing skeletal elements using combination micro-CT imaging, molecular profiling clonal cell tracing. find that, contrast development, regenerative growth accomplished based entirely on cartilage expansion prior ossification, not limiting transversal resulting bulkier parts. The oriented...
The WNT/β-catenin signaling pathway plays a central role in the biology of periodontium, yet function specific extracellular WNT ligands remains poorly understood. By using Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that ligand WNT1 is strong promoter cementum bone formation vivo. We induced Wnt1 expression for 1, 3, or 9 wk Wnt1Tg mice analyzed them at age 6 12 wk. Micro–computed tomography (CT)...