A5066848145- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Developmental Biology and Gene Regulation
- Zebrafish Biomedical Research Applications
- Crystallography and molecular interactions
- Congenital heart defects research
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Neurobiology and Insect Physiology Research
- Photoreceptor and optogenetics research
- Neural dynamics and brain function
- Animal Genetics and Reproduction
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- TGF-β signaling in diseases
- Sleep and Wakefulness Research
- RNA modifications and cancer
- Wnt/β-catenin signaling in development and cancer
- Retinal Development and Disorders
- Organometallic Complex Synthesis and Catalysis
- Hedgehog Signaling Pathway Studies
University of Basel
1994-2025
Harvard University
2014-2024
Broad Institute
2013-2024
University of Washington
2001-2024
Center for Systems Biology
2012-2024
Allen Institute
2017-2023
Seattle University
2019-2021
Harvard Stem Cell Institute
2011-2020
Massachusetts Institute of Technology
2005-2019
Center for Pain and the Brain
2015-2019
MicroRNAs (miRNAs) comprise 1 to 3% of all vertebrate genes, but their in vivo functions and mechanisms action remain largely unknown. Zebrafish miR-430 is expressed at the onset zygotic transcription regulates morphogenesis during early development. By using a microarray approach target validation, we find that directly several hundred messenger RNA molecules (mRNAs). Most targets are maternally mRNAs accumulate absence miR-430. We also show accelerates deadenylation mRNAs. These results...
Systematic genome-wide mutagenesis screens for embryonic phenotypes have been instrumental in the understanding of invertebrate and plant development. Here, we report results from first application such a large-scale genetic screening to vertebrate Male zebrafish were mutagenized with N-ethyl N-nitrosourea induce mutations spermatogonial cells at an average specific locus rate one 651 genomes. Mutations transmitted F1 generation, 2205 F2 families raised. F3 embryos sibling crosses within...
MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZ ) mutants disrupt the Dicer ribonuclease III and double-stranded RNA-binding domains. Mutant embryos do not process precursor miRNAs into mature miRNAs, but injection of preprocessed restores silencing, indicating disrupted domains dispensable for later steps silencing. MZ undergo axis differentiate multiple cell types...
The CRISPR/Cas9 system has been implemented in a variety of model organisms to mediate site-directed mutagenesis. A wide range mutation rates reported, but at limited number genomic target sites. To uncover the rules that govern effective Cas9-mediated mutagenesis zebrafish, we targeted over hundred loci for using streamlined and cloning-free method. We generated mutations 85% genes with varying across several orders magnitude, identified sequence composition influence increased by...
During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these trajectories during zebrafish we sequenced 38,731 and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the of 25 cell types early somitogenesis, gene expression along them, their spatial origin in blastula. Analysis Nodal signaling mutants revealed that transcriptomes were canalized into subset wild-type trajectories. Some...
Long noncoding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in humans and the mouse have annotated lncRNAs expressed cell lines adult tissues, systematic analysis during vertebrate embryogenesis has been elusive. To identify with potential functions embryogenesis, we performed time-series RNA-seq experiments at eight stages early zebrafish development. We reconstructed 56,535 high-confidence...
A major obstacle for the discovery of psychoactive drugs is inability to predict how small molecules will alter complex behaviors. We report development and application a high-throughput, quantitative screen that behavior larval zebrafish. found multidimensional nature observed phenotypes enabled hierarchical clustering according shared Behavioral profiling revealed conserved functions psychotropic predicted mechanisms action poorly characterized compounds. In addition, behavioral implicated...
The zebrafish EGF-CFC gene one-eyed pinhead (oep) is required zygotically for the formation of ventral neuroectoderm, endoderm, and prechordal plate. Here we report that embryos lacking both maternal zygotic Oep activity are defective in germ layer formation, organizer development, positioning anterior-posterior axis. An identical phenotype displayed by double mutants nodal-related genes squint cyclops. Mutations oep eliminate response to Squint Cyclops overexpression but suppressed...
INTRODUCTION The developmental path by which a fertilized egg gives rise to the cells of multicellular organism is termed cell lineage. In 1983, John Sulston and colleagues documented invariant lineage roundworm Caenorhabditis elegans as determined visual observation. However, tracing in nearly all other organisms vastly more challenging. Contemporary methods rely on genetic markers or somatic mutations, but these approaches have limitations that preclude their application at level whole,...
Cilia, as motile and sensory organelles, have been implicated in normal development, well diseases including cystic kidney disease, hydrocephalus situs inversus. In epithelia, cilia are proposed to be non-motile while the mouse node, two populations, regulate situs. We show that zebrafish larval kidney, spinal cord Kupffer's vesicle motile, suggesting fluid flow is a common feature of each these organs. Disruption structure or motility resulted pronephric cyst formation, left-right asymmetry...
ABSTRACT As part of a large-scale mutagenesis screen the zebrafish genome, we have identified 58 mutations that affect formation and function cardiovascular system. The system is particularly amenable for screening in transparent embryo because heart blood vessels are prominent their easily examined. We classified affecting into those primarily either morphogenesis or function. Nine clearly disrupt heart. cloche deletes endocardium. In mutants, myocardial layer forms absence endocardium but...
It has been assumed that most, if not all, signals regulating early development have identified. Contrary to this expectation, we identified 28 candidate signaling proteins expressed during zebrafish embryogenesis, including Toddler, a short, conserved, and secreted peptide. Both absence overproduction of Toddler reduce the movement mesendodermal cells gastrulation. Local ubiquitous production promote cell movement, suggesting is neither an attractant nor repellent but acts globally as...
MicroRNAs (miRNAs) repress hundreds of target messenger RNAs (mRNAs), but the physiological roles specific miRNA-mRNA interactions remain largely elusive. We report that zebrafish microRNA-430 (miR-430) dampens and balances expression transforming growth factor-beta (TGF-beta) Nodal agonist squint TGF-beta antagonist lefty. To disrupt interaction pairs, we developed protector morpholinos complementary to miRNA binding sites in mRNAs. Protection or lefty mRNAs from miR-430 resulted enhanced...
Abstract We studied the efficiency with which two chemical mutagens, ethyl methanesulfonate (EMS) and N-ethyl-N-nitrosourea (ENU) can induce mutations at different stages of spermatogenesis in zebrafish (Brachydanio rerio). Both EMS ENU induced high rates post-meiotic germ cells, as indicated by incidence F1 progeny mosaic for albino mutation. For pre-meiotic however, only was found to be an effective mutagen, frequencies non-mosaic mutant four pigmentation loci. Several mutagenic regimens...
As many as 10% of humans suffer chronic sleep disturbances, yet the genetic mechanisms that regulate remain essentially unknown. It is therefore crucial to develop simple and cost-effective vertebrate models study regulation sleep. The best characterized mammalian sleep/wake regulator hypocretin/orexin (Hcrt), whose loss results in disorder narcolepsy has also been implicated feeding behavior, energy homeostasis, thermoregulation, reward seeking, addiction, maternal behavior. Here we report...