RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6

Nature, Journal Year: 2018, Volume and Issue: 557(7706), P. 564 - 569

Published: May 1, 2018

Language: Английский

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<b><i>Xenopus</i></b>: An Undervalued Model Organism to Study and Model Human Genetic Disease

Cells Tissues Organs, Journal Year: 2018, Volume and Issue: 205(5-6), P. 303 - 313

Published: Jan. 1, 2018

The function of normal and defective candidate genes for human genetic diseases, which are rapidly being identified in large numbers by geneticists the biomedical community at large, will be best studied relevant predictive model organisms that allow high-speed verification, analysis underlying developmental, cellular molecular mechanisms, establishment disease models to test therapeutic options. We describe discuss pros cons frog Xenopus, has been extensively used uncover developmental mechanisms past, but is underutilized as a model. argue Xenopus complements more commonly mouse zebrafish time- cost-efficient animal study alleles mechanisms.

Language: Английский

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Melanin deposition and key molecular features in Xenopus tropicalis oocytes

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 27, 2025

Melanin pigmentation in oocytes is a critical feature for both the esthetic and developmental aspects of oocytes, influencing their polarity overall development. Despite substantial knowledge melanogenesis melanocytes retinal pigment epithelium cells, molecular mechanisms underlying oocyte remain largely unknown. Here, we compare wild-type, tyr−/− mitf−/− Xenopus tropicalis found that exhibit normal melanin deposition at animal pole, whereas show no this site. Transmission electron microscopy confirmed proceeds normally, similar to wild-type oocytes. Transcriptomic analysis revealed still express melanogenesis-related genes, enabling them complete melanogenesis. Additionally, expression MiT subfamily factor tfe3 relatively high, while tfeb, mitf, tfec levels are extremely low. The pattern tyr other genes. Thus, independent Mitf may be regulated by factors such as Tfe3, which control genes like tyr, dct, tyrp1. Furthermore, transcriptomic data changes related mitochondrial cloud formation represent most significant during Overall, these findings suggest further elucidation Tyr-dependent Mitf-independent pole will enhance our understanding Oogenesis.

Language: Английский

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Tissue-Specific Gene Inactivation inXenopus laevis: Knockout oflhx1in the Kidney with CRISPR/Cas9

Genetics, Journal Year: 2017, Volume and Issue: 208(2), P. 673 - 686

Published: Nov. 30, 2017

Abstract Xenopus laevis is a classic developmental model, but its allotetraploid genome has limited our ability to perform genetic manipulations. The advance of... Studying genes involved in organogenesis often difficult because many of these are also essential for early development. frog, laevis, commonly used study processes, the presence two homeologs genes, it been use as model. Few studies have successfully CRISPR amphibians, and currently there no tissue-targeted knockout strategy described Xenopus. goal this determine whether CRISPR/Cas9-mediated gene can be targeted kidney without perturbing function. We demonstrate that targeting editing eye F0 embryos feasible. Our shows both lhx1 results disruption development function does not lead defects. Therefore, may necessary bypass defects reported upon Lhx1 protein expression or by morpholinos, antisense RNA, dominant negative constructs. establish control (slc45a2) when knocked out albinism altering This establishes feasibility tissue-specific Xenopus, providing cost-effective efficient method assessing roles implicated abnormalities amenable high-throughput drug screening techniques.

Language: Английский

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Activated Signaling Pathways and Targeted Therapies in Desmoid-Type Fibromatosis: A Literature Review

Frontiers in Oncology, Journal Year: 2019, Volume and Issue: 9

Published: May 17, 2019

Desmoid-type fibromatosis (DTF) is a rare, soft tissue tumor of mesenchymal origin which characterized by local infiltrative growth behavior. Besides "wait and see", surgery radiotherapy, several systemic treatments are available for symptomatic patients. Recently, targeted therapies being explored in DTF. Unfortunately, effective treatment still hampered the limited knowledge molecular mechanisms that prompt DTF tumorigenesis. Many studies focus on Wnt/β-catenin signaling, since vast majority tumors harbors mutation CTNNB1 gene or APC gene. The established role pathway forms an attractive therapeutic target, however, drugs targeting this experimental stage not yet clinic. Only few address other signaling pathways can drive uncontrolled such as: JAK/STAT, Notch, PI3 kinase/AKT, mTOR, Hedgehog, estrogen regulatory pathways. Evidence involvement these tumorigenesis predominantly based expression levels key genes, observed clinical responses after treatment. No clear driver has been identified, rationale often lacking. In review, we highlight common active provide up-to-date overview their potential.

Language: Английский

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Maximizing CRISPR/Cas9 phenotype penetrance applying predictive modeling of editing outcomes in Xenopus and zebrafish embryos

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Sept. 4, 2020

Abstract CRISPR/Cas9 genome editing has revolutionized functional genomics in vertebrates. However, edited F 0 animals too often demonstrate variable phenotypic penetrance due to the mosaic nature of outcomes after double strand break (DSB) repair. Even with high efficiency levels editing, phenotypes may be obscured by proportional presence in-frame mutations that still produce protein. Recently, studies cell culture systems have shown CRISPR/Cas9-mediated can dependent on local sequence context and predicted computational methods. Here, we similar approaches used forecast gene Xenopus tropicalis , laevis, zebrafish. We show a publicly available neural network previously trained mouse embryonic stem cultures (InDelphi-mESC) is able accurately predict early vertebrate embryos. Our observations direct implications for experiment design, allowing selection guide RNAs repair outcome signatures enriched towards frameshift mutations, maximization phenotype generation.

Language: Английский

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CRISPR/Cas9 disease models in zebrafish and Xenopus: The genetic renaissance of fish and frogs

Drug Discovery Today Technologies, Journal Year: 2018, Volume and Issue: 28, P. 41 - 52

Published: July 31, 2018

Language: Английский

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Advances in the Xenopus immunome: Diversification, expansion, and contraction

Developmental & Comparative Immunology, Journal Year: 2023, Volume and Issue: 145, P. 104734 - 104734

Published: May 10, 2023

Language: Английский

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Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders

Brain, Journal Year: 2023, Volume and Issue: 147(4), P. 1436 - 1456

Published: Nov. 9, 2023

The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins regulates N-myristoylation via N-myristoyltransferase enzymes (NMTs). However, its precise function cells still unclear, as consequence ACBD6 defects on human pathophysiology. Using exome sequencing extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants ACBD6. We generated zebrafish Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 characterized myristic acid alkyne (YnMyr) chemical proteomics model organisms cells, latter also being subjected further to peroxisomal localization studies. (23 males 22 females), aged 1-50 years, typically present complex progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%) mild cerebellar ataxia (85%) associated gait (94%), limb spasticity/hypertonia (76%), oculomotor (71%) behavioural abnormalities (65%), overweight (59%), microcephaly (39%) epilepsy (33%). most conspicuous common disorder was dystonia frequently leading early-onset postural deformities (55%) cervical (31%). A jerky tremor upper limbs (63%), head parkinsonism/hypokinesia developing advancing age (32%) simple motor vocal tics were among other frequent disorders. Midline brain malformations including corpus callosum (70%), hypoplasia/agenesis anterior commissure (66%), short midbrain small inferior vermis (38% each) well hypertrophy clava (24%) neuroimaging findings. Acbd6-deficient models effectively recapitulated many clinical phenotypes reported patients disorders, neuromotor impairment, seizures, microcephaly, craniofacial accompanied delay increased mortality over time. Unlike ACBD5, did not show ACBD6-deficiency altered parameters patient fibroblasts. Significant differences YnMyr-labelling observed for 68 co- 18 post-translationally N-myristoylated patient-derived similarly acbd6-deficient X. models, Fus, Marcks Chchd-related implicated neurological diseases. study provides evidence that pathogenic lead distinct neurodevelopmental syndrome cognitive

Language: Английский

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The Amphibian Genomics Consortium: advancing genomic and genetic resources for amphibian research and conservation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding features this animal class that other terrestrial vertebrates. The need for genomic resources is more urgent than ever due to increasing threats group. are one most imperiled taxonomic groups, with approximately 41% species threatened extinction habitat loss, changes in land use patterns, disease, climate change, synergistic effects. Amphibian have provided better ontogenetic diversity, tissue regeneration, life history reproductive modes, antipredator strategies, resilience adaptive responses. They also serve as essential models studying broad traits, such evolutionary genome expansions contractions, they exhibit widest range sizes among all taxa possess multiple mechanisms genetic sex determination. Despite these features, sequencing amphibians has significantly lagged behind vertebrates, primarily challenges assembling large, repeat-rich genomes relative lack societal support. emergence long-read technologies, combined advanced molecular computational techniques improve scaffolding reduce workloads, now making it possible address some challenges. To promote accelerate production research international coordination collaboration, we launched Genomics Consortium (AGC, https://mvs.unimelb.edu.au/amphibian-genomics-consortium) early 2023. This burgeoning community already 282 members from 41 countries. AGC aims leverage capabilities its advance bridge implementation gap biologists, bioinformaticians, conservation practitioners. Here evaluate state field genomics, highlight previous studies, present overcome, call on communities unite part enable "leap" next level.

Language: Английский

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