A5000913635- Developmental Biology and Gene Regulation
- Cellular Mechanics and Interactions
- Renal and related cancers
- Cancer Cells and Metastasis
- Pluripotent Stem Cells Research
- Gene Regulatory Network Analysis
- Genetic and Kidney Cyst Diseases
- Neonatal Respiratory Health Research
- Single-cell and spatial transcriptomics
- Hippo pathway signaling and YAP/TAZ
- Bacterial Genetics and Biotechnology
- Neurogenesis and neuroplasticity mechanisms
- 3D Printing in Biomedical Research
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Mathematical Biology Tumor Growth
- Microtubule and mitosis dynamics
- Pancreatic function and diabetes
- Cell Image Analysis Techniques
- RNA Research and Splicing
- Congenital heart defects research
- Microbial Metabolic Engineering and Bioproduction
- Monoclonal and Polyclonal Antibodies Research
- Planarian Biology and Electrostimulation
- RNA and protein synthesis mechanisms
SIB Swiss Institute of Bioinformatics
2016-2025
ETH Zurich
2016-2025
Board of the Swiss Federal Institutes of Technology
2020
University of Lausanne
2018
University of Oxford
2006
Imperial Valley College
2006
MRC Laboratory of Molecular Biology
2001-2005
Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to 2-cell stage embryo. However, whether and how such asymmetries arise embryo is unclear. Here, we performed prospective tracing human embryos using live imaging, non-invasive cell labeling, computational predictions determine contribution each blastomere epiblast (body), hypoblast (yolk sac), trophectoderm (placenta). We show majority cells originate from only one observe three...
Abstract Malignancies of epithelial tissues, called carcinomas, account for most cancer cases. Research has largely focused on correlating different carcinoma subtypes to genetic alterations. However, as well a rewiring in the signalling networks, progression is accompanied by mechanical changes cells and extracellular matrix. Here we reveal intricate morphologies basement membrane at onset bladder propose that they emerge from instability upon overgrowth. We imaged mouse human tissue...
Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail is remarkably stereotyped. tree generated by sequential, non-random use three geometrically simple modes (domain branching, planar orthogonal bifurcation). While many regulatory components local interactions have defined an integrated understanding network that controls lacking....
BMP signaling plays a crucial role in the establishment of dorso-ventral body axis bilaterally symmetric animals. However, topologies bone morphogenetic protein (BMP) networks vary drastically different animal groups, raising questions about evolutionary constraints and evolvability systems. Using loss-of-function analysis mathematical modeling, we show that two centers expressing BMPs antagonists maintain secondary sea anemone Nematostella. We demonstrate is required for asymmetric Hox gene...
Neural stem cells (NSCs) in the adult mouse hippocampal dentate gyrus (DG) are mostly quiescent, and only a few cell cycle at any point time. DG NSCs become increasingly dormant with age enter mitosis less frequently, which impinges on neurogenesis. How NSC inactivity is maintained largely unknown. Here, we found that Id4 downstream target of Notch2 signaling maintains quiescence by blocking cell-cycle entry. expression sufficient to promote knockdown rescues Notch2-induced inhibition...
Abstract The three-dimensional (3D) organization of cells determines tissue function and integrity, changes markedly in development disease. Cell-based simulations have long been used to define the underlying mechanical principles. However, high computational costs so far limited either simplified cell geometries or small patches. Here, we present SimuCell3D, an efficient open-source program simulate large tissues three dimensions with subcellular resolution, growth, proliferation,...
Journal Article An analysis of B cell selection mechanisms in germinal centers Get access Michael E. Meyer-Hermann, Meyer-Hermann **Email: m.meyer-hermann@fias.uni-frankfurt.de Search for other works by this author on: Oxford Academic Google Scholar Philip K. Maini, Maini Dagmar Iber Mathematical Medicine and Biology: A the IMA, Volume 23, Issue 3, September 2006, Pages 255–277, https://doi.org/10.1093/imammb/dql012 Published: 01 2006
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...
Early branching events during lung development are stereotyped. Although key regulatory components have been defined, the mechanism remains elusive. We now used a developmental series of 3D geometric datasets mouse embryonic lungs as well time-lapse movies cultured to obtain physiological geometries and displacement fields. find that only ligand-receptor-based Turing model in combination with particular geometry effect arises from distinct expression domains ligands receptors successfully...
Turing models have been proposed to explain the emergence of digits during limb development. However, so far molecular components that would give rise patterns are elusive. We recently shown a particular type receptor-ligand interaction can Schnakenberg-type patterns, which reproduce patterning lung and kidney branching morphogenesis. Recent knockout experiments identified Smad4 as key protein in digit patterning. show here BMP-receptor meets conditions for pattern, resulting model...
Branching patterns and regulatory networks differ between branched organs. It has remained unclear whether a common mechanism exists how organ-specific can emerge. Of all previously proposed signalling-based mechanisms, only ligand-receptor-based Turing based on FGF10 SHH quantitatively recapitulates the lung branching patterns. We now show that GDNF-dependent of cultured wildtype mutant ureteric buds, achieves similar when directing domain outgrowth in silico. further predict confirm...
Abstract Motivation: The simulation of morphogenetic problems requires the simultaneous and coupled signalling tissue dynamics. A cellular resolution domain is important to adequately describe impact cell-based events, such as cell division, cell–cell interactions spatially restricted events. tightly mechano-regulatory tool therefore required. Results: We developed an open-source software framework for problems. environment offers core functionalities models. In addition, great flexibility...
During morphogenesis, epithelial sheets remodel into complex geometries. How cells dynamically organise their contact with neighbouring in these tightly packed tissues is poorly understood. We have used light-sheet microscopy of growing mouse embryonic lung explants, three-dimensional cell segmentation, and physical theory to unravel the principles behind 3D organisation pseudostratified epithelia. find that highly irregular shapes exhibit numerous neighbour intercalations along apical-basal...
Abstract Neural stem cells (NSCs) generate neurons of the cerebral cortex with distinct morphologies and functions. How specific neuron production, differentiation migration are orchestrated is unclear. Hippo signaling regulates gene expression through Tead transcription factors (TFs). We show that transcriptional coactivators Yap1/Taz Teads have functions during cortical development. promote NSC maintenance Satb2 + production at expense Tbr1 generation. However, moderate effects on do not...
Abstract Morphogen gradients encode positional information during development. How high patterning precision is achieved despite natural variation in both the morphogen and readout process, still largely elusive. Here, we show that error of mouse neural tube has previously been overestimated, reported accuracy central progenitor domain boundaries can be with a single gradient, rather than requiring simultaneous opposing gradients. Consistently independently, numerical simulations based on...
Organoids are self-organized three-dimensional (3D) multicellular tissue cultures which derive from cancerous and healthy stem cells, sharing a highly similarity to the corresponding in vivo organs. Since their introduction 2009, they have emerged as valuable model for studying early embryogenesis, organ development, well tools drug screening, disease modeling personalized therapy. can now be established various tissues, including brain, retina, thyroid, gastrointestinal, lung, liver,...
We present PolyHoop, a lightweight standalone C++ implementation of mechanical model to simulate the dynamics soft particles and cellular tissues in two dimensions. With only few geometrical physical parameters, PolyHoop is capable simulating wide range particulate matter systems: from biological cells vesicles, bubbles, foams, emulsions, other amorphous materials. The or are represented by continuously remodeling, non-convex, high-resolution polygons that can undergo growth, division,...
During embryonic and adult neurogenesis, neural stem cells (NSCs) generate the correct number types of neurons in a temporospatial fashion. Control NSC activity fate is crucial for brain formation homeostasis. Neurogenesis differ considerably, but Notch signaling inhibitor DNA-binding (ID) factors are pivotal both. ID regulate maintenance; however, it has been difficult to evaluate how these pathways potentially interact. Here, we combined mathematical modeling with analysis single-cell...
The main signalling proteins that control early kidney branching have been defined. Yet the underlying mechanism is still elusive. We previously shown a Schnakenberg-type Turing can recapitulate and protein expression patterns in wildtype mutant lungs, but it unclear whether this would extend to other branched organs are regulated by proteins. Here we show GDNF-RET regulatory interaction gives rise model reproduces observed budding of ureteric bud from Wolffian duct, its invasion into...