A5089253797- Sleep and Wakefulness Research
- Zebrafish Biomedical Research Applications
- Circadian rhythm and melatonin
- Thyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Regulation of Appetite and Obesity
- Congenital heart defects research
- Birth, Development, and Health
- Photoreceptor and optogenetics research
- RNA modifications and cancer
- Fibroblast Growth Factor Research
- Pancreatic function and diabetes
- Neonatal Health and Biochemistry
- Genetic Syndromes and Imprinting
- Pregnancy and preeclampsia studies
- Fish Ecology and Management Studies
- Retinoids in leukemia and cellular processes
- Mitochondrial Function and Pathology
- Physiological and biochemical adaptations
- RNA Research and Splicing
- interferon and immune responses
- Microtubule and mitosis dynamics
- Adipose Tissue and Metabolism
Weizmann Institute of Science
2024-2025
Bar-Ilan University
2012-2024
Massachusetts Institute of Technology
2015
Abstract Sleep is essential to all animals with a nervous system. Nevertheless, the core cellular function of sleep unknown, and there no conserved molecular marker define across phylogeny. Time-lapse imaging chromosomal markers in single cells live zebrafish revealed that increases chromosome dynamics individual neurons but not two other cell types. Manipulation sleep, dynamics, neuronal activity, DNA double-strand breaks (DSBs) showed are low number DSBs accumulates during wakefulness. In...
The mechanisms and treatment of psychomotor retardation, which includes motor cognitive impairment, are indefinite. Allan-Herndon-Dudley syndrome (AHDS) is an X-linked retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated mutations the monocarboxylate transporter 8 (mct8/slc16a2) gene, a TH transporter. In order to determine...
Fragile X syndrome (FXS) is the most frequent inherited form of mental retardation. The cause for this X-linked disorder silencing fragile retardation 1 (fmr1) gene and absence protein (Fmrp). RNA-binding Fmrp represses translation, particularly in synapses. In Drosophila, interacts with adenosine deaminase acting on RNA (Adar) enzymes. Adar enzymes convert to inosine (A-to-I) modify sequence transcripts. Utilizing fmr1 zebrafish mutant (fmr1-/-), we studied Fmrp-dependent neuronal circuit...
Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor retardation characterized by neurological impairment and abnormal thyroid hormone (TH) levels. Mutations in the TH transporter, monocarboxylate transporter 8 (MCT8), are associated with AHDS. MCT8 knock-out mice exhibit impaired levels; however, they lack defects. Here, zebrafish mct8 gene promoter were isolated, promoter-driven transgenic lines used to show that, similar humans, primarily expressed nervous vascular systems....
ABSTRACT Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS), psychomotor retardation associated with mutations in the thyroid-hormone (TH) transporter MCT8 (monocarboxylate 8). AHDS characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8−/−) zebrafish model. The quantification genetic markers oligodendrocyte progenitor cells...
Sleep has been conserved throughout evolution; however, the molecular and neuronal mechanisms of sleep are largely unknown. The hypothalamic hypocretin/orexin (Hcrt) neurons regulate sleep\wake states, feeding, stress, reward. To elucidate mechanism that enables these various functions to identify regulators, we combined fluorescence cell sorting RNA-seq in hcrt:EGFP zebrafish. Dozens Hcrt-neuron–specific transcripts were identified comprehensive high-resolution imaging revealed...
Organisms evolve mechanisms that regulate the properties of biogenic crystals to support a wide range functions, from vision and camouflage communication thermal regulation. Yet, mechanism underlying formation diverse intracellular remains enigmatic. Here we unravel biochemical control over crystal morphogenesis in zebrafish iridophores. We show chemical composition determines their shape, particularly through ratio between nucleobases guanine hypoxanthine. reveal these variations are...
Pigmentation plays a vital role in the survival of organisms, supporting functions such as camouflage, communication, and mate attraction. In vertebrates, these are mediated by specialized pigment cells known chromatophores which, uric acid crystal-forming leucophores remain least understood, with little about their molecular mechanisms. A key question cell biology is whether different crystal chemistries require distinct pathways, or similar cellular processes drive formation diverse...
Neurotensin (NTS) is a 13 amino acid neuropeptide that expressed in the hypothalamus. In mammals, NTS-producing neurons express leptin receptor (LepRb) regulate function of hypocretin/orexin (HCRT) and dopamine neurons. Thus, hypothalamic leptin-NTS-HCRT neuronal network orchestrates key homeostatic output, including sleep, feeding, reward. However, intricate mechanisms circuitry unique role NTS-expressing remain unclear. We studied NTS networks zebrafish cloned genes encoding (NTSR)....
Neuronal-activity-regulated pentraxin (NARP/NPTX2/NP2) is a secreted synaptic protein that regulates the trafficking of glutamate receptors and mediates learning, memory, drug addiction. The role NPTX2 in regulating structural plasticity behavior developing vertebrate indefinite. We characterized expression nptx2a larvae adult zebrafish established transcription activator-like effector nuclease (TALEN)-mediated mutant (nptx2a-/-) to study Nptx2a behavior. Similar mammals, was expressed...
Background: The thyroid hormones (THs) triiodothyronine (T3) and thyroxine (T4) are crucial regulators of brain development function. Cell-specific transporter proteins facilitate TH uptake efflux across the cell membrane, insufficient transport causes hypothyroidism mental retardation. Mutations in transporters monocarboxylate 8 (MCT8, SLC16A2) organic anion-transporting polypeptide 1C1 (OATP1C1, SLCO1C1) associated with psychomotor retardation Allan-Herndon-Dudley syndrome juvenile...
Brain nuclei are traditionally defined by their anatomy, activity, and expression of specific markers. The hypothalamus contains discrete neuronal populations that coordinate fundamental behavioral functions, including sleep wakefulness, in all vertebrates. Particularly, the diverse roles hypocretin/orexin (Hcrt)-releasing neurons suggest functional heterogeneity among Hcrt neurons. Using single-cell RNA sequencing (scRNA-seq) high-resolution imaging adult male female zebrafish hypothalamic...
Thyroid hormones (THs; T3 and T4) enter cells using specific transporters regulate development metabolism. Mutation in the TH transporter monocarboxylate 8 (MCT8, SLC16A2) is associated with brain hypothyroidism neurological impairment. We established mct8 mutant (mct8-/-) zebrafish as a model for MCT8 deficiency, which causes endocrinological, neurological, behavioral alterations. Here, we profiled transcriptome of mct8-/- larvae. Among hundreds differentially expressed genes, expression...
Thyroid hormones (THs), thyroxine (T4), and triiodothyronine (T3), regulate growth, metabolism, neurodevelopment. THs secretion is controlled by the pituitary thyroid-stimulating hormone (TSH) hypothalamic–pituitary–thyroid (HPT) axis. The organic anion-transporting polypeptide 1C1 (OATP1C1/SLCO1C1) monocarboxylate transporter 8 (MCT8/SLC16A2) actively transport THs, which bind to their nuclear receptors induce gene expression. A mutation in OATP1C1 associated with brain hypometabolism,...
<b><i>Background:</i></b> Hypothalamic neurotensin (Nts)-secreting neurons regulate fundamental physiological processes including metabolism and feeding. However, the role of Nts in modulation locomotor activity, sleep, arousal is unclear. We previously identified characterized zebrafish hypothalamus. <b><i>Materials Methods:</i></b> In order to study Nts, <i>nts</i> mutant (<i>nts</i>–/–), overexpressing were generated....
Hypothyroidism is a common pathological condition characterized by insufficient activity of the thyroid hormones (THs), thyroxine (T4), and 3,5,3'-triiodothyronine (T3), in whole body or specific tissues. associated with inadequate development intestine as well gastrointestinal diseases. We used zebrafish model hypothyroidism to identify characterize TH-modulated genes cellular pathways controlling development. In hypothyroid juveniles adults, number mucus-secreting goblet cells was reduced,...