Applications & Publications
Technical Notes
3D Tomographic Visualization of Zebrafish Larvae Using the VAST BioImager™ (QTN-026)
March 13, 2020
Publications
m6A-mRNA Reader YTHDF2 Identified as a Potential Risk Gene in Autism With Disproportionate Megalencephaly
Nishizaki et al. January 30, 2025 https://doi.org/10.1002/aur.3314
View Abstractm6A-mRNA Reader YTHDF2 Identified as a Potential Risk Gene in Autism With Disproportionate Megalencephaly
Among autistic individuals, a subphenotype of disproportionate megalencephaly (ASD-DM) seen at three years of age is associated with co-occurring intellectual disability and poorer prognoses later in life. However, many of the genes contributing to ASD-DM have yet to be delineated. In this study, we identified additional ASD-DM candidate genes with the aim to better define the genetic etiology of this subphenotype of autism. We expanded the previously studied sample size of ASD-DM individuals ten fold by including probands from the Autism Phenome Project and Simons Simplex Collection, totaling 766 autistic individuals meeting the criteria for megalencephaly or macrocephaly and revealing 154 candidate ASD-DM genes harboring de novo protein-impacting variants. Our findings include 14 high confidence autism genes and seven genes previously associated with DM. Five impacted genes have previously been associated with both autism and DM, including CHD8 and PTEN. By performing functional network analysis, we expanded to additional candidate genes, including one previously implicated in ASD-DM (PIK3CA) as well as 184 additional genes connected with ASD or DM alone. Using zebrafish, we modeled a de novo tandem duplication impacting YTHDF2, encoding an N6-methyladenosine (m6A)-mRNA reader, in an ASD-DM proband. Testing zebrafish CRISPR knockdown led to reduced head/brain size, while overexpressing YTHDF2 resulted in increased head/brain size matching that of the proband. Single-cell transcriptomes of YTHDF2 gain-of-function larvae point to reduced expression of Fragile-X-syndrome-associated FMRP-target genes globally and in the developing brain, providing insight into the mechanism underlying autistic phenotypes. We additionally discovered a variant impacting a different gene encoding an m6A reader, YTHDC1, in our ASD-DM cohort. Though we highlight only two cases to date, our study provides support for the m6A-RNA modification pathway as potentially contributing to this severe form of autism.
The zebrafish embryo as a model for chemically-induced steatosis: A case study with three pesticides
Heusinkveld et al. August 14, 2024 Toxicology,Volume 508,2024,153927,ISSN 0300-483X,https://doi.org/10.1016/j.tox.2024.153927.(https://www.sciencedirect.com/science/article/pii/S0300483X24002087)
The zebrafish embryo as a model for chemically-induced steatosis: A case study with three pesticides
Adaptive Optics in an Oblique Plane Microscope
McFadden et al. March 22, 2024 bioRxiv 2024.03.21.586191; doi: https://doi.org/10.1101/2024.03.21.586191
Adaptive Optics in an Oblique Plane Microscope
A retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression
Ghosh et al. February 15, 2024 Cell, Volume 187, Issue 4p814-830.e23,February 15, 2024
View AbstractA retroviral link to vertebrate myelination through retrotransposon-RNA-mediated control of myelin gene expression
Myelin, the insulating sheath that surrounds neuronal axons, is produced by oligodendrocytes in the central nervous system (CNS). This evolutionary innovation, which first appears in jawed vertebrates, enabled rapid transmission of nerve impulses, more complex brains, and greater morphological diversity. Here, we report that RNA-level expression of RNLTR12-int, a retrotransposon of retroviral origin, is essential for myelination. We show that RNLTR12-int-encoded RNA binds to the transcription factor SOX10 to regulate transcription of myelin basic protein (Mbp, the major constituent of myelin) in rodents. RNLTR12-int-like sequences (which we name RetroMyelin) are found in all jawed vertebrates, and we further demonstrate their function in regulating myelination in two different vertebrate classes (zebrafish and frogs). Our study therefore suggests that retroviral endogenization played a prominent role in the emergence of vertebrate myelin.
Analysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity
Nöth et al. December 21, 2023 Reproductive Toxicology, Open access, Published: 21 December 2023, Volume 98, pages 537–549, (2024)
View AbstractAnalysis of vascular disruption in zebrafish embryos as an endpoint to predict developmental toxicity
Inhibition of angiogenesis is an important mode of action for the teratogenic effect of chemicals and drugs. There is a gap in the availability of simple, experimental screening models for the detection of angiogenesis inhibition. The zebrafish embryo represents an alternative test system which offers the complexity of developmental differentiation of an entire organism while allowing for small-scale and high-throughput screening. Here we present a novel automated imaging-based method to detect the inhibition of angiogenesis in early life stage zebrafish. Video subtraction was used to identify the location and number of functional intersegmental vessels according to the detection of moving blood cells. By exposing embryos to multiple tyrosine kinase inhibitors including SU4312, SU5416, Sorafenib, or PTK787, we confirmed that this method can detect concentration-dependent inhibition of angiogenesis. Parallel assessment of arterial and venal aorta ruled out a potential bias by impaired heart or blood cell development. In contrast, the histone deacetylase inhibitor valproic acid did not affect ISV formation supporting the specificity of the angiogenic effects. The new test method showed higher sensitivity, i.e. lower effect concentrations, relative to a fluorescent reporter gene strain (Tg(KDR:EGFP)) exposed to the same tyrosine kinase inhibitors indicating that functional effects due to altered tubulogenesis or blood transport can be detected before structural changes of the endothelium are visible by fluorescence imaging. Comparison of exposure windows indicated higher specificity for angiogenesis when exposure started at later embryonic stages (24 h post-fertilization). One of the test compounds was showing particularly high specificity for angiogenesis effects (SU4312) and was, therefore, suggested as a model compound for the identification of molecular markers of angiogenic disruption. Our findings establish video imaging in wild-type strains as viable, non-invasive, high-throughput method for the detection of chemical-induced angiogenic disruption in zebrafish embryos.
Grouping of chemicals into mode of action classes by automated effect pattern analysis using the zebrafish embryo toxicity test
Teixidó et al. March 07, 2022 Reproductive Toxicology, Open Access, Volume 96, pages 1353–1369, Published: 07 March 2022
View AbstractGrouping of chemicals into mode of action classes by automated effect pattern analysis using the zebrafish embryo toxicity test
Automated in vivo drug screen in zebrafish identifies synapse-stabilising drugs with relevance to spinal muscular atrophy
Oprisoreanu et al. April 26, 2021 Dis Model Mech (2021) 14 (4): dmm047761. https://doi.org/10.1242/dmm.047761
Automated in vivo drug screen in zebrafish identifies synapse-stabilising drugs with relevance to spinal muscular atrophy
Assessment of Autism Zebrafish Mutant Models Using a High-Throughput Larval Phenotyping Platform
Colón-Rodríguez A, et al. November 23, 2020 Front. Cell Dev. Biol. 8:586296.; doi: 10.3389/fcell.2020.586296
Assessment of Autism Zebrafish Mutant Models Using a High-Throughput Larval Phenotyping Platform
Morphometric analysis of developing zebrafish embryos allow predicting teratogenicity modes of action in higher vertebrates
Jarque et al. August 19, 2020 Reproductive Toxicology 96 (2020) 337-348; https://doi.org/10.1016/j.reprotox.2020.08.004
Morphometric analysis of developing zebrafish embryos allow predicting teratogenicity modes of action in higher vertebrates
Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/ Cas9-based approach
von der Heyde et al. July 16, 2020 Sci Rep 10, 11831 (2020). https://doi.org/10.1038/s41598-020-68567-1
Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/ Cas9-based approach
TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci
Davis et al. July 03, 2020 Human Molecular Genetics, , ddaa120, https://doi.org/10.1093/hmg/ddaa120
TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci
Integrative discovery of treatments for high-risk neuroblastoma
Almstedt et al. January 03, 2020 Nat Commun. 2020 Jan 3;11(1):71. doi: 10.1038/s41467-019-13817-8.
Integrative discovery of treatments for high-risk neuroblastoma
The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension
Morikawa et al. November 12, 2019 Science Signaling 12 Nov 2019: Vol. 12, Issue 607, eaay4430 DOI: 10.1126/scisignal.aay4430
The ALK-1/SMAD/ATOH8 axis attenuates hypoxic responses and protects against the development of pulmonary arterial hypertension
Comparison of Zebrafish Larvae and hiPSC Cardiomyocytes for Predicting Drug-Induced Cardiotoxicity in Humans
Sylvia Dyballa et al. October 01, 2019 Toxicological Sciences, Volume 171, Issue 2, October 2019, Pages 283–295, https://doi.org/10.1093/toxsci/kfz165
Comparison of Zebrafish Larvae and hiPSC Cardiomyocytes for Predicting Drug-Induced Cardiotoxicity in Humans
TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish
Gudmundsson et al. September 01, 2019 Sci Rep. 2019; 9: 10730. Published online 2019 Jul 24. doi: 10.1038/s41598-019-46632-8
TAF1, associated with intellectual disability in humans, is essential for embryogenesis and regulates neurodevelopmental processes in zebrafish
Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis
Bandaru et al. June 11, 2019 bioRxiv 502674; doi: https://doi.org/10.1101/502674
Zebrafish larvae as a model system for systematic characterization of drugs and genes in dyslipidemia and atherosclerosis
Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features
Ansar et al. May 09, 2019 https://doi.org/10.1016/j.ajhg.2019.04.002
Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features
An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos’
Jarque et al. August 29, 2018 PLOS ONE | https://doi.org/10.1371/journal.pone.0203087 August 29, 2018
An automated screening method for detecting compounds with goitrogenic activity using transgenic zebrafish embryos’
An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination
Early et al. July 06, 2018 DOI: 10.7554/eLife.35136 DOI: 10.7554/eLife.35136
An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination
Three-dimensional reconstruction and measurements of zebrafish larvae from high-throughput axial-view in vivo imaging
Guo et al. April 26, 2017 https://doi.org/10.1364/BOE.8.002611; Received 9 Nov 2016; revised 31 Jan 2017; accepted 31 Jan 2017; published 26 Apr 2017
Three-dimensional reconstruction and measurements of zebrafish larvae from high-throughput axial-view in vivo imaging
A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis.
Frosk et al. March 06, 2017 J Med Genet. 2017 Mar 6. pii: jmedgenet-2016-104296. doi: 10.1136/jmedgenet-2016-104296. [Epub ahead of print]
A truncating mutation in CEP55 is the likely cause of MARCH, a novel syndrome affecting neuronal mitosis.
SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
Shaw et al. January 09, 2017 Nature Genetics (2017) doi:10.1038/ng.3743
SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome
De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder
Kury et al. January 03, 2017 http://dx.doi.org/10.1016/j.ajhg.2017.01.003
De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder
Developing systems for high-throughput screening of infectious diseases using zebrafish
Veneman, Wouter Jurjen December 05, 2015 Department of Animal Sciences and Health, Institute of Biology, Faculty of Science, Leiden University
Developing systems for high-throughput screening of infectious diseases using zebrafish
Mutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.
Mala Isrie 1,2 et al. October 14, 2015 Am J Hum Genet. 2015 Dec 3;97(6):790-800. doi: 10.1016/j.ajhg.2015.10.014.
View AbstractMutations in Either TUBB or MAPRE2 Cause Circumferential Skin Creases Kunze Type.
1Center for Human Genetics, University Hospitals Leuven, 3000 Leuven, Belgium; 2Laboratory for Genetics of Cognition, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium
Semi-automated detection of goitrogenic compounds using transgenic zebrafish embryos and the VAST BioImager platform
SETAC Europe 25th Annual Meeting
Sergio Jarque¹, Eva Fetter², Marek Pípal¹, Marie Smutná¹, Ludek Blaha¹, Stefan Scholz².
May 03, 2015
Semi-automated detection of goitrogenic compounds using transgenic zebrafish embryos and the VAST BioImager platform
1RECETOX, Masaryk University, Faculty of Science, Kamenice 753/5, 625 00, Brno
2Department of Bioanalytical Ecotoxicology, Helmholtz Centre for Environmental Research – UFZ, Permoserstraße 15, 04318 Leipzig, Germany
Establishment and optimization of a high throughput setup to study Staphylococcus epidermidis and Mycobacterium marinum infection as a model for drug discovery.
Veneman WJ¹, Marín-Juez R², de Sonneville J³, Ordas A4, Jong-Raadsen S², Meijer AH4, Spaink HP5. June 26, 2014 JOVE
View AbstractEstablishment and optimization of a high throughput setup to study Staphylococcus epidermidis and Mycobacterium marinum infection as a model for drug discovery.
1Institute of Biology, Leiden University; w.j.veneman@biology.leidenuniv.nl. 2ZF-screens BV. 3Life Science Methods BV. 4Institute of Biology, Leiden University. 5Institute of Biology, Leiden University
High-throughput hyperdimensional vertebrate phenotyping
Carlos Pardo-Martin, Amin Allalou, Jaime Medina, Peter M. Eimon, Carolina Wählby Mehmet Fatih Yanik February 12, 2013 Nature Communications 4, Article number:1467, doi:10.1038/ncomms2475
High-throughput hyperdimensional vertebrate phenotyping
Presenting VAST BioImager™: A new modular, expandable platform to automate the orientation of 2-7 day old zebrafish larvae for imaging
The Nordic Countries Zebrafish Meeting on the Zebrafish as a model for Development and Disease
Union Biometrica, Geel, Belgium, Union Biometrica, Holliston, MA, USA
Yanik lab, MIT, Boston, MA, USA
November 21, 2012
Presenting VAST BioImager™: A new modular, expandable platform to automate the orientation of 2-7 day old zebrafish larvae for imaging
Fully automated cellular-resolution vertebrate screening platform with parallel animal processing
Chang TY, Pardo-Martin C, Allalou A, Wählby C, Yanik MF. February 01, 2012 Lab Chip. 2012 Feb 21;12(4):711-6. doi: 10.1039/c1lc20849g. Epub 2011 Dec 8.
Fully automated cellular-resolution vertebrate screening platform with parallel animal processing
High-throughput in vivo vertebrate screening.
Pardo-Martin C, Chang TY, Koo BK, Gilleland CL, Wasserman SC, Yanik MF. August 01, 2010 Nat Methods. 2010 Aug;7(8):634-6. doi: 10.1038/nmeth.1481. Epub 2010 Jul 18.