Genomics, convergent neuroscience and progress in understanding autism spectrum disorder

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(6), P. 323 - 341

Published: April 19, 2022

Language: Английский

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Xenbase: key features and resources of the Xenopus model organism knowledgebase

Genetics, Journal Year: 2023, Volume and Issue: 224(1)

Published: Feb. 9, 2023

Abstract Xenbase (https://www.xenbase.org/), the Xenopus model organism knowledgebase, is a web-accessible resource that integrates diverse genomic and biological data from research on laboratory frogs laevis tropicalis. The goal of to accelerate discovery empower research, enhance impact data, facilitate dissemination these data. also enhances value through high-quality curation, integration, providing bioinformatics tools optimized for experiments, linking human other organisms. plays an indispensable role in making interoperable accessible broader biomedical community accordance with FAIR principles. provides annotated updates organizations such as NCBI, UniProtKB, Ensembl, Gene Ontology consortium, most recently, Alliance Genomic Resources, common clearing house humans This article brief overview key recently added features Xenbase. New include processing high-throughput sequencing NCBI Expression Omnibus; curation anatomical, physiological, expression phenotypes newly created Phenotype Ontology; annotations; new anatomical drawings Normal Table development; integration latest v10.1 genome annotations. Finally, we highlight areas future development at continue support community.

Language: Английский

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Parallel in vivo analysis of large-effect autism genes implicates cortical neurogenesis and estrogen in risk and resilience

Neuron, Journal Year: 2021, Volume and Issue: 109(5), P. 788 - 804.e8

Published: Jan. 25, 2021

Language: Английский

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Autism gene variants disrupt enteric neuron migration and cause gastrointestinal dysmotility

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 6, 2025

The co-occurrence of autism and gastrointestinal distress is well-established, yet the molecular underpinnings remain unknown. identification high-confidence, large-effect genes offers opportunity to identify convergent, underlying biology by studying these in context system. Here we show that expression enriched human prenatal gut neurons their migratory progenitors, suggesting development and/or function may be disrupted autism-associated genetic variants, leading dysfunction. document prevalence issues patients with variants sixteen genes, highlighting dysmotility, consistent potential enteric neuron Using Xenopus tropicalis, individually target five (SYNGAP1, CHD8, SCN2A, CHD2, DYRK1A) observe neuronal progenitor migration for each. Further analysis DYRK1A reveals perturbation causes dysmotility vivo, which can ameliorated treatment either two serotonin signaling modulators, identified vivo drug screening. This work suggests atypical contributes commonly seen individuals a productive therapeutic pathway.

Language: Английский

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Translational Neuroscience Approaches to Understanding Autism

American Journal of Psychiatry, Journal Year: 2023, Volume and Issue: 180(4), P. 265 - 276

Published: April 1, 2023

While autism spectrum disorder affects nearly 2% of children in the United States, little is known with certainty concerning etiologies and brain systems involved. This due, part, to substantial heterogeneity presentation core symptoms as well great number co-occurring conditions that are common autistic individuals. Understanding neurobiology further hampered by limited availability postmortem tissue determine cellular molecular alterations take place brain. Animal models therefore provide translational value helping define neural constitute social mediate repetitive behaviors or interests. If they based on genetic environmental factors contribute autism, organisms from flies nonhuman primates may serve structure function Ultimately, successful can also be employed test safety effectiveness potential therapeutics. an overview major animal species currently used including appraisal advantages limitations each.

Language: Английский

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Assessing the impact of antiviral drugs commonly utilized during the COVID-19 pandemic on the embryonic development of Xenopus laevis

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 472, P. 134462 - 134462

Published: April 28, 2024

Language: Английский

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A convergent molecular network underlying autism and congenital heart disease

Cell Systems, Journal Year: 2021, Volume and Issue: 12(11), P. 1094 - 1107.e6

Published: Aug. 18, 2021

Language: Английский

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HCN2 channel‐induced rescue of brain, eye, heart and gut teratogenesis caused by nicotine, ethanol and aberrant notch signalling

Wound Repair and Regeneration, Journal Year: 2022, Volume and Issue: 30(6), P. 681 - 706

Published: June 4, 2022

Organogenesis is a complex process that can be disrupted by embryonic exposure to teratogens or mutation-induced alterations in signalling pathways, both of which result organ mispatterning. Building on prior work Xenopus laevis showed increased HCN2 ion channel activity rescues nicotine-induced brain and eye morphogenesis, we demonstrate much broader HCN2-based rescue patterning defects. Induced expression local distant tissues CNS (brain eye) as well non-CNS (heart gut) defects induced three different teratogenic conditions: nicotine exposure, ethanol aberrant Notch protein. Rescue also small-molecule activators, even with delayed treatment initiation. Our results suggest (likely mediated bioelectric signals) an effective regulator organogenesis from all germ layers (ectoderm, mesoderm endoderm) reveal non-cell-autonomous influences formation at considerable distance during development. These molecular strategies for repair could explored the future regenerative medicine.

Language: Английский

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Interaction between perfluoro‐octanoic sulfonate and common antibiotics induces developmental anomalies and lethality in Xenopus laevis

Developmental Dynamics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Abstract Background Perfluoroalkyl substances (PFAS) are persistent environmental contaminants previously used for industrial purposes as a non‐stick coating and flame retardant. The stability of these molecules prevents their breakdown, which results in ground water contamination across the globe. known to bioaccumulate various organisms. However, health consequences remain unclear due large number PFAS family different effects on tissues. Here, we use frog Xenopus laevis investigate developmental exposure molecule perfluoro‐octanoic sulfonate (PFOS). Results We find that high levels PFOS significant axial shortening developing tadpoles. Further, dose‐dependent formation cellular mass dorsal fin. Unexpectedly, found phenotypes exacerbated upon co‐exposure with commonly antibiotics. Specifically, gentamicin co‐treatment increased apoptosis, loss integrity, overall lethality. Conclusions Our suggest mechanism whereby reaches toxic mitochondria only presence PFOS. These findings add our understanding vertebrate development present an added concern potential interactions

Language: Английский

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Use of the alternative test R-FETAX (Refined-Frog Embryo Teratogenicity Assay-Xenopus) to evaluate the Fetal Alcohol Spectrum Disorders (FASD)

Reproductive Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 108896 - 108896

Published: March 1, 2025

Fetal Alcohol Spectrum Disorders (FASD) refer to a range of conditions in children caused by alcohol consumption during pregnancy, including morphological defects, developmental delays, and neurobehavioral impairments. Ethanol (EtOH) at high concentrations (1-3% v/v) was shown induce malformations lethality Xenopus laevis embryos exposed throughout the FETAX test (from mid-blastula stage final pre-feeding larval stage). The aim this work evaluate multiple effects EtOH exposure (0.1-3% using R-FETAX protocol. Embryos obtained through natural mating were specific windows: organogenetic period (sensitive abnormalities) neurodevelopmental window behavioral alterations). Additional groups either entire duration (classical exposure) or for brief 4-hour before end (acute exposure). Lethality monitored over six-day period. At conclusion test, functional deglutition performed, external gross morphology as well delays (FETAX-score method) assessed. Neurobehavioral swimming conducted only on tadpoles considered normal evaluation. Dose-response relationships modeled PROAST software derive benchmark dose levels, with response set levels used points departure risk assessment. findings demonstrated dose- stage-specific that mimic FASD symptoms observed humans. These results emphasize no amount can be safe development.

Language: Английский

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