ArticleACS chemical neuroscience2019
Bypassing Glutamic Acid Decarboxylase 1 (Gad1) Induced Craniofacial Defects with a Photoactivatable Translation Blocker Morpholino.
Article in ACS chemical neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Developmental dynamics of catshark cranial neural crest cells provide insights into gnathostome facial evolution.Development (Cambridge, England) · 2026Article
- The Quinoline Photoremovable Group (PPG) Platform-A Medicinal Chemist's Approach for Photocage Development and Applications.Medicinal research reviews · 2025Review
- Decreased GABA levels during development result in increased connectivity in the larval zebrafish tectum.bioRxiv : the preprint server for biology · 2024Article
- Development of label-free light-controlled gene expression technologies using mid-IR and terahertz light.Frontiers in bioengineering and biotechnology · 2024Review
- Multi-Photon-Sensitive Chromophore for the Photorelease of Biologically Active Phenols.ACS chemical neuroscience · 2023Article
- Antisense Oligonucleotide Activation via Enzymatic Antibiotic Resistance Mechanism.ACS chemical biology · 2023Article
- Direct Detection of the Photorearrangement Reaction of Quinoline-Protected Dialkylanilines.Photochemistry and photobiology · 2022Article
- Translational control of gene function through optically regulated nucleic acids.Chemical Society reviews · 2021Review
- Conditionally Activated ("Caged") Oligonucleotides.Molecules (Basel, Switzerland) · 2021Review
- Caspase-Activated Oligonucleotide Probe.Bioconjugate chemistry · 2020Article
- Controlling gene expression with light: a multidisciplinary endeavour.Biochemical Society transactions · 2020Review
- Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.Brain : a journal of neurology · 2020Article
- Practical Synthesis of Quinoline-Protected Morpholino Oligomers for Light-Triggered Regulation of Gene Function.Molecules (Basel, Switzerland) · 2020Article
- Photoactivatable Dopamine and Sulpiride to Explore the Function of Dopaminergic Neurons and Circuits.ACS chemical neuroscience · 2020Article
- Pyridoxamine Supplementation Effectively Reverses the Abnormal Phenotypes of Zebrafish Larvae With PNPO Deficiency.Frontiers in pharmacology · 2019Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
γ-Amino butyric acid (GABA) mediated signaling is critical in the central and enteric nervous systems, pancreas, lungs, and other tissues. It is associated with many neurological disorders and craniofacial development. Glutamic acid decarboxylase (GAD) synthesizes GABA from glutamate, and knockdown of the gad1 gene results in craniofacial defects that are lethal in zebrafish. To bypass this and enable observation of the neurological defects resulting from knocking down gad1 expression, a photoactivatable morpholino oligonucleotide (MO) against gad1 was prepared by cyclization with a photocleavable linker rendering the MO inactive. The cyclized MO was stable in the dark and toward degradative enzymes and was completely linearized upon brief exposure to 405 nm light. In the course of investigating the function of the ccMOs in zebrafish, we discovered that zebrafish possess paralogous gad1 genes, gad1a and gad1b. A gad1b MO injected at the 1-4 cell stage caused severe morphological defects in head development, which could be bypassed, enabling the fish to develop normally, if the fish were injected with a photoactivatable, cyclized gad1b MO and grown in the dark. At 1 day post fertilization (dpf), light activation of the gad1b MO followed by observation at 3 and 7 dpf led to increased and abnormal electrophysiological brain activity compared to wild type animals. The photocleavable linker can be used to cyclize and inactivate any MO, and represents a general strategy to parse the function of developmentally important genes in a spatiotemporal manner.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.