A5031342395- Zebrafish Biomedical Research Applications
- Barrier Structure and Function Studies
- Retinal Development and Disorders
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Photoreceptor and optogenetics research
- Glioma Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Neuroscience and Neuropharmacology Research
- Cardiomyopathy and Myosin Studies
- Infant Nutrition and Health
- Neurogenesis and neuroplasticity mechanisms
- MicroRNA in disease regulation
- Pediatric health and respiratory diseases
- Monoclonal and Polyclonal Antibodies Research
- Developmental Biology and Gene Regulation
- RNA Research and Splicing
- Pregnancy and preeclampsia studies
- Circadian rhythm and melatonin
- Connexins and lens biology
- RNA modifications and cancer
- Tracheal and airway disorders
- Cell Adhesion Molecules Research
- Chromatin Remodeling and Cancer
- Cleft Lip and Palate Research
University of Wisconsin–Madison
2015-2025
St. Jude Children's Research Hospital
2010-2024
Hospital for Sick Children
1992-2019
SickKids Foundation
2016-2019
University of Toronto
2012-2019
University of Calgary
1990-2015
Cincinnati Children's Hospital Medical Center
2014
University of California, San Francisco
2005-2008
University of Washington
2000-2007
Neurological Surgery
2005-2007
The blood-brain barrier (BBB) plays a vital role in the central nervous system (CNS). A comprehensive understanding of BBB development has been hampered by difficulties observing differentiation brain endothelial cells (BECs) real-time. Here, we generated two transgenic zebrafish line, Tg(glut1b:mCherry) and Tg(plvap:EGFP), to serve as vivo reporters development. We showed that barriergenesis (i.e. induction BEC differentiation) occurs immediately tips migrate into parenchyma. Using...
Hearing loss caused by aging, noise, cisplatin toxicity, or other insults affects 360 million people worldwide, but there are no Food and Drug Administration-approved drugs to prevent treat it. We screened 4,385 small molecules in a cochlear cell line identified 10 compounds that protected against toxicity mouse explants. Among them, kenpaullone, an inhibitor of multiple kinases, including cyclin-dependent kinase 2 (CDK2), zebrafish lateral-line neuromasts from and, when delivered locally,...
Lactadherin, a major glycoprotein of the human milk fat globule membrane, is abundant in breast and expressed carcinomas. Previously, we have shown that mature protein, formerly known as BA46, has three domains: an epidermal growth factor (EGF)-like domain containing Arg-Gly-Asp (RGD) cell adhesion sequence C1 C2 domains similar to those found coagulation factors V VIII. An alignment lactadherin with its bovine (MGP57/53) murine (MFG-E8) homologs shows RGD been conserved during evolution,...
Summary: Methods: Seizures were induced with pentylenetetrazole (PTZ). Zebrafish analyzed between 3 and 7 days postfertilization (dpf). Genome mutations in founders by using N‐ ethyl‐nitrosourea (ENU). Seizure behavior was monitored a high‐speed camera quantified locomotion‐tracking software. Electrographic activity field‐recording electrode placed the optic tectum of agar‐immobilized zebrafish. Results: Short‐term PTZ exposure elicited burst‐suppression seizure pattern 3‐dpf zebrafish more...
During neuroinflammation, the proinflammatory cytokine interleukin-1β (IL-1β) impacts blood-brain barrier (BBB) function by disrupting brain endothelial tight junctions, promoting vascular permeability, and increasing transmigration of immune cells. Here, we examined effects Il-1β on
Transducins couple visual pigments to cGMP hydrolysis, the only recognized phototransduction pathway in vertebrate photoreceptors. Here we describe a zebrafish mutant, no optokinetic response f(w21) (nof), with nonsense mutation gene encoding alpha subunit of cone transducin. Retinal morphology and levels enzymes are normal nof retinas, but transducin is undetectable. Dark current cones also normal, it insensitive moderate intensity light. The do respond, however, bright These responses...
To identify in vivo a promoter fragment that specifically directs transgene expression all zebrafish cone photoreceptors. This subsequently enables GFP labeling of cones for facile morphologic analysis and purification genetic rescue achromatopsia.Promoter fragments the transducin alpha (TalphaC) gene were subcloned upstream EGFP microinjected into one- to two-cell-stage embryos. Promoter activity was assessed by fluorescence microscopy wholemounts retinal cryosections, photoreceptors...
Neuronal connections are often arranged in layers, which divided into sublaminae harboring synapses with similar response properties. It is still debated how fine-grained synaptic layering established during development. Here we investigated two stratified areas of the zebrafish visual pathway, inner plexiform layer (IPL) retina and neuropil optic tectum, determined if activity required for their organization.The IPL 5-day-old larvae composed at least nine sublaminae, comprising between...
Bone Morphogenetic Proteins (BMPs) are morphogens that play a major role in regulating development and homeostasis. Although BMPs used for the treatment of bone kidney disorders, their clinical use is limited due to supra-physiological doses required therapeutic efficacy causing severe side effects. Because recombinant expensive produce, small molecule activators BMP signaling would be cost-effective alternative with added benefit being potentially more easily deliverable. Here, we report...
Zebrafish have been used as a vertebrate model to study human cancers such melanoma, rhabdomyosarcoma, liver cancer, and leukemia well for high-throughput screening of small molecules therapeutic value. However, they are just emerging brain tumors, which among the most devastating difficult treat. In this study, we evaluated zebrafish tumor by overexpressing version oncogenic KRAS (KRAS(G12V)).Using cytokeratin 5 (krt5) glial fibrillary acidic protein (gfap) gene promoters, activated Ras...
The central nervous system (CNS) requires specialized blood vessels to support neural function within specific microenvironments. During neurovascular development, endothelial Wnt/β-catenin signaling is required for BBB development the brain parenchyma, whereas fenestrated that lack properties do not require signaling. Here, we used zebrafish further characterize this phenotypic heterogeneity of CNS vasculature. Using transgenic reporters transcriptional activity, found an inverse...
Defects in the pyruvate dehydrogenase (PDH) complex result severe neurological dysfunction, congenital lactic acidosis, growth retardation, and early death. Current treatments for PDH deficiency are administered postnatally generally unsuccessful. Because many patients with this disease born irreversible defects, a model system development of effective pre- postnatal therapies would be great value. In behavioral genetic screen aimed to identify zebrafish visual function we previously...
The blood–brain barrier (BBB) restricts the delivery of therapeutics into central nervous system (CNS). This limitation is due largely to localization drug transport mechanisms brain endothelial cells (BECs). Although mammalian and in vitro models are currently used study transport, zebrafish (Danio rerio) advantageous for dissecting complex biological problems such as BBB. report focuses on a suitable model studying BBB transport. Clinical Pharmacology & Therapeutics (2012); 92 5, 567–570....
Mutations in the human CACNA1F gene cause incomplete congenital stationary night blindness type 2 (CSNB2), a non-progressive, clinically heterogeneous retinal disorder. However, molecular mechanisms underlying CSNB2 have not been fully explored. Here, we describe positional cloning of blind zebrafish mutant, wait until dark (wud), which encodes homolog CACNA1F. We identified two cacna1f paralogs and showed that cacna1fa transcript (the mutated wud) is expressed exclusively photoreceptor...
The choroid plexus, an epithelial-based structure localized in the brain ventricle, is major component of blood-cerebrospinal fluid barrier. plexus produces cerebrospinal and regulates components fluid. Abnormal function associated with neurodegenerative diseases, tumor formation epithelium, hydrocephaly. In this study, we used zebrafish (Danio rerio) as a model system to understand genetic development. We generated enhancer trap line, Et(cp:EGFP)sj2, that expresses enhanced green...
The BA46 antigen of the human milk fat globule (HMFG) membrane is expressed in breast carcinomas and has been used successfully as a target for experimental cancer radioimmunotherapy. To characterize this further, we obtained entire cDNA sequence focused on its possible role cell adhesion. derived protein encodes 387-residue precursor composed putative signal peptide, an amino-terminal epidermal growth factor (EGF)-like domain containing adhesion tripeptide arginine–glycine–aspartic acid...
Dysregulation of Sonic hedgehog (Shh) signaling has been implicated in glioma pathogenesis. Yet, the role this pathway gliomagenesis remains controversial because lack relevant animal models. Using cytokeratin 5 promoter, we ectopically expressed a constitutively active zebrafish Smoothened (Smoa1) neural progenitor cells and analyzed tumorigenic capacity activated Shh both transient stable transgenic fish. Transient fish overexpressing Smoa1 developed retinal brain tumors, suggesting smoa1...
Abstract The zebrafish has become an important model for cancer research. Several models have been established by transgenic expression of human or mouse oncogenes in zebrafish. Since it is amenable to efficient transgenesis, immense potential be used studying interaction and pathways at the organismal level. Using Gal4VP16-UAS binary approach, we stable lines expressing EGFP fusion protein activated Smoothened (Smoa1-EGFP). Expression Smoa1-EGFP itself did not lead tumor formation either...
The high mobility group transcription factor SOX9 is expressed in stem cells, progenitor and differentiated cell-types developing mature organs. Exposure to a variety of toxicants including dioxin, di(2-ethylhexyl) phthalate, 6:2 chlorinated polyfluorinated ether sulfonate, chlorpyrifos results the downregulation tetrapod Sox9 and/or zebrafish sox9b. Disruption Sox9/sox9b function through environmental exposures or genetic mutations produce wide range phenotypes adversely affect organ...
Abstract The zebrafish mutant, partial optokinetic response b (pob), was isolated using an N-ethyl N-nitrosourea (ENU)-based screening strategy designed to identify larvae with defective responses in red but not white light. Previous studies showed that red-light blindness pob is due the specific loss of long-wavelength photoreceptor cells via apoptotic mechanism. Here, we used positional cloning mutated gene. We find encodes a highly conserved 30-kDa protein unknown function. To demonstrate...