A5080499335- Neurogenesis and neuroplasticity mechanisms
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neuropharmacology Research
- CRISPR and Genetic Engineering
- Genetic Syndromes and Imprinting
- FOXO transcription factor regulation
- Cell Image Analysis Techniques
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Congenital heart defects research
- Circular RNAs in diseases
- Glioma Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Prenatal Screening and Diagnostics
- Cellular Mechanics and Interactions
- Developmental Biology and Gene Regulation
- GDF15 and Related Biomarkers
- Animal Genetics and Reproduction
- Cardiomyopathy and Myosin Studies
Institute of Science and Technology Austria
2016-2025
Howard Hughes Medical Institute
2010-2020
Stanford University
2010-2020
University of Basel
2002-2007
Friedrich Miescher Institute
2004-2007
Two ETS transcription factors of the Pea3 subfamily are induced in subpopulations dorsal root ganglion (DRG) sensory and spinal motor neurons by target-derived factors. Their expression controls late aspects neuronal differentiation such as target invasion branching. Here, we show that onset gene is an essential requirement for normal neuron differentiation. We provide genetic evidence mouse precocious DRG perturbs axonal projections, acquisition terminal markers, their dependence on...
Radial glial progenitors (RGPs) are responsible for producing nearly all neocortical neurons. To gain insight into the patterns of RGP division and neuron production, we quantitatively analyzed excitatory genesis in mouse neocortex using Mosaic Analysis with Double Markers, which provides single-cell resolution progenitor potential vivo. We found that RGPs progress through a coherent program their proliferative diminishes predictable manner. Upon entry neurogenic phase, individual produce...
During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage molecular identities successive generations apical progenitors (APs) and their daughter in mouse embryos. identified a core set evolutionarily conserved, genes that drive APs internally driven more exteroceptive states. found...
Significance The nature of postnatal cardiomyogenesis in mammals remains dispute. Here, we provide cell-level evidence for the birth cardiomyocytes newborn and adult mice. Our clonal analysis, based on mosaic analysis with double markers mouse model, shows that are parent cell origin generated postnatally. findings confirm limited, symmetric division is a rare phenomenon heart after birth.
Microinjection of recombinant DNA into zygotic pronuclei has been widely used for producing transgenic mice. However, with this method, the insertion site, integrity, and copy number transgene cannot be controlled. Here, we present an integrase-based approach to produce mice via pronuclear injection, whereby intact single-copy can inserted predetermined chromosomal loci high efficiency (up 40%), faithfully transmitted through generations. We show that neighboring elements bacterial within...
Abstract To reveal the full potential of human pluripotent stem cells, new methods for rapid, site-specific genomic engineering are needed. Here, we describe a system precise genetic modification embryonic cells (ESCs) and induced (iPSCs). We identified novel locus, H11, located in safe, intergenic, transcriptionally active region chromosome 22, as recipient site, to provide robust, ubiquitous expression inserted genes. Recipient cell lines were established by placement ‘landing pad’...
Adult neural stem cells and multiciliated ependymal are glial essential for neurological functions. Together, they make up the adult neurogenic niche. Using both high-throughput clonal analysis single-cell resolution of progenitor division patterns fate, we show that these two components niche lineally related: sister to cells, whereas most arise from terminal symmetric divisions lineage. Unexpectedly, found antagonist regulators DNA replication, GemC1 Geminin, can tune proportion cells. Our...
Neurotrophins regulate diverse aspects of neuronal development and plasticity, but their precise in vivo functions during neural circuit assembly the central brain remain unclear. We show that neurotrophin receptor tropomyosin-related kinase C (TrkC) is required for dendritic growth branching mouse cerebellar Purkinje cells. Sparse TrkC knockout reduced dendrite complexity, global cell had no effect. Removal ligand neurotrophin-3 (NT-3) from granule cells, which provide major afferent input...
The cerebral cortex contains multiple areas with distinctive cytoarchitectonic patterns, but the cellular mechanisms underlying emergence of this diversity remain unclear. Here, we have investigated neuronal output individual progenitor cells in developing mouse neocortex using a combination methods that together circumvent biases and limitations approaches. Our experimental results indicate generate pyramidal cell lineages wide range sizes laminar configurations. Mathematical modeling...
Branching morphogenesis of the epithelial ureteric bud forms renal collecting duct system and is critical for normal nephron number, while low number implicated in hypertension disease. Ureteric growth branching requires GDNF signaling from surrounding mesenchyme to cells at tips, via Ret receptor tyrosine kinase coreceptor Gfrα1; up-regulates transcription factors Etv4 Etv5, which are also branching. Despite extensive knowledge genetic control these events, it not understood, cellular...
Mosaic analysis with double markers (MADM) offers one approach to visualize and concomitantly manipulate genetically defined cells in mice single-cell resolution. MADM applications include the of lineage, morphology physiology, genomic imprinting phenotypes, dissection cell-autonomous gene functions vivo health disease. Yet, can only be applied <25% all mouse genes on select chromosomes date. To overcome this limitation, we generate transgenic knocked-in cassettes near centromeres 19...
Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries behavior. Inspired by discovery mutations SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead autism, we employed metabolomic profiling study states cerebral cortex across different developmental stages. We found forebrain undergoes significant remodeling throughout development,...
Nestin-cre transgenic mice have been widely used to direct recombination neural stem cells (NSCs) and intermediate progenitor (NPCs). Here we report that a readily utilized, the only commercially available, line is insufficient for directing in early embryonic NSCs NPCs. Analysis of efficiency multiple cre-dependent reporters genetic mosaic revealed consistent temporal spatial patterns For comparison utilized knock-in Emx1(cre) found robust NPCs ventricular subventricular zones cerebral...
In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped the blastocyst stage preimplantation development. Here, we address this by integrating transcriptomic epigenomic approaches in mouse embryos. We find that seventy-one...
Abstract Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within few days. Here, we characterized biomechanics of LN swelling on cellular organ scale. We identified lymphocyte trapping by influx proliferation as drivers an outward pressure force, causing T-zone (TRCs) their...