Neurobehavioral phenotypes in the pan-neuronal GAL4 zebrafish line Tg(elavl3:KalTA4)
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PROVIDER: PRJNA1216611 | ENA |
REPOSITORIES: ENA
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Project description:The Gal4/UAS system is used across model organisms to overexpress target genes in precise cell types and relies on generating transgenic Gal4 driver lines. In zebrafish, the Tg(elavl3:KalTA4) (HuC) line drives robust expression in neurons. We observed an increased prevalence of swim bladder defects in Tg(elavl3:KalTA4) zebrafish larvae compared to wildtype siblings, which prompted us to investigate whether transgenic larvae display additional neurobehavioral phenotypes. Tg(elavl3:KalTA4) larvae showed alterations in brain activity, brain morphology, and behavior, including increased hindbrain size and reduced activity of the cerebellum. Bulk RNA-seq analysis revealed massive dysregulation of the transcriptome and suggested an increased ratio of neuronal progenitor cells compared to differentiated neurons. To understand whether these phenotypes derive from Gal4 toxicity or from positional effects related to transgenesis, we used economical low-pass whole genome sequencing to map the Tol2-mediated insertion site to chromosome eight. Reduced expression of the neighboring gene gadd45ga, a known cell cycle regulator, is consistent with increased proliferation and suggests a role for positional effects. Challenges with creating alternative pan-neuronal lines include the length of the elavl3 (HuC) promoter (9 kb) and random insertion using traditional transgenesis methods. To facilitate the generation of alternative lines, we cloned five neuronal promoters (atp6v0cb, elavl3, rtn1a, sncb, and stmn1b) ranging from 1.7 kb to 4.3 kb and created KalTA4 lines using Tol2 and the phiC31 integrase-based pIGLET system. Our study highlights the importance of using appropriate genetic controls and establishes a roadmap for identifying positional effects in new transgenic lines.
2025-02-04 | GSE288775 | GEO
Project description:The Gal4/UAS system is used across model organisms to overexpress target genes in precise cell types and relies on generating transgenic Gal4 driver lines. In zebrafish, the Tg(elavl3:KalTA4) (HuC) line drives robust expression in neurons. We observed an increased prevalence of swim bladder defects in Tg(elavl3:KalTA4) zebrafish larvae compared to wildtype siblings, which prompted us to investigate whether transgenic larvae display additional neurobehavioral phenotypes. Tg(elavl3:KalTA4) larvae showed alterations in brain activity, brain morphology, and behavior, including increased hindbrain size and reduced activity of the cerebellum. Bulk RNA-seq analysis revealed massive dysregulation of the transcriptome and suggested an increased ratio of neuronal progenitor cells compared to differentiated neurons. To understand whether these phenotypes derive from Gal4 toxicity or from positional effects related to transgenesis, we used economical low-pass whole genome sequencing to map the Tol2-mediated insertion site to chromosome eight. Reduced expression of the neighboring gene gadd45ga, a known cell cycle regulator, is consistent with increased proliferation and suggests a role for positional effects. Challenges with creating alternative pan-neuronal lines include the length of the elavl3 (HuC) promoter (9 kb) and random insertion using traditional transgenesis methods. To facilitate the generation of alternative lines, we cloned five neuronal promoters (atp6v0cb, elavl3, rtn1a, sncb, and stmn1b) ranging from 1.7 kb to 4.3 kb and created KalTA4 lines using Tol2 and the phiC31 integrase-based pIGLET system. Our study highlights the importance of using appropriate genetic controls and establishes a roadmap for identifying positional effects in new transgenic lines.
2025-02-02 | GSE288241 | GEO
Project description:Here we demonstrated that the RNA-binding protein ELAVL3 is specifically upregulated in NEPC, and that overexpression of ELAVL3 alone sufficiently induce neuroendocrine phenotype in prostate adenocarcinoma. We performed RIP-seq of ELAVL3-V5 from PC3 cell lines.
2023-10-23 | GSE236365 | GEO
Project description:Neuronal Elavl-like (nElavl) RNA binding proteins have three paralogs (Elavl2, Elavl3 and Elavl4) in the mouse genome. This family of RNABPs have been implicated in a variety of post-transcriptional RNA processing mechanisms, including regulation of mRNA stability, alternative splicing, and translational regulation. In this study, using mouse exon arrays, we identify significant differences (p<0.01) in 119 transcripts between wild-type and Elavl3/Elavl4 double knockout forebrain tissue at postnatal day 0. A total of 10 samples were analyzed. These samples consisted of 5 littermate pairs of wild-type and Elavl3/Elavl4 double knockout mice.
2013-01-05 | E-GEOD-43287 | biostudies-arrayexpress
Project description:Here we demonstrated that the RNA-binding protein ELAVL3 is specifically upregulated in NEPC, and that overexpression of ELAVL3 alone sufficiently induce neuroendocrine phenotype in prostate adenocarcinoma. We performed RIP-seq of ELAVL3-V5 from 2 prostate cancer cell lines.
2023-10-23 | GSE224910 | GEO
Project description:Here we demonstrated that the RNA-binding protein ELAVL3 is specifically upregulated in NEPC, and that overexpression of ELAVL3 alone sufficiently induce neuroendocrine phenotype in prostate adenocarcinoma. Pharmacological inhibition of ELAVL3 with pyrvinium pamoate, an FDA-approved drug, effectively suppressed tumor growth, reduced the risk of metastases, and improved the survival of NEPC mice models.
2023-10-23 | GSE222469 | GEO
Project description:Here we demonstrated that the RNA-binding protein ELAVL3 is specifically upregulated in NEPC, and that overexpression of ELAVL3 alone sufficiently induce neuroendocrine phenotype in prostate adenocarcinoma. Pharmacological inhibition of ELAVL3 with pyrvinium pamoate, an FDA-approved drug, effectively suppressed tumor growth, reduced the risk of metastases, and improved the survival of NEPC mice models.
2023-10-23 | GSE224909 | GEO
Project description:Neuronal Elavl-like (nElavl) RNA binding proteins have three paralogs (Elavl2, Elavl3 and Elavl4) in the mouse genome. This family of RNABPs have been implicated in a variety of post-transcriptional RNA processing mechanisms, including regulation of mRNA stability, alternative splicing, and translational regulation. In this study, using mouse exon arrays, we identify significant differences (p<0.01) in 119 transcripts between wild-type and Elavl3/Elavl4 double knockout forebrain tissue at postnatal day 0.
2013-01-05 | GSE43287 | GEO
Project description:Promoter-specific transcriptional activators (activators) stimulate transcription through direct interactions with one or more components of the transcription machinery, termed the “target”. Previous studies have provided evidence that the Tra1 subunit of the yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) complex is the target of the yeast activator Gal4. However, several other general transcription factors, in particular the mediator complex, have also been implicated as Gal4 targets. To investigate the essentiality of Tra1 as a target of Gal4, here we derive Tra1 mutants that are selectively defective for interaction with Gal4 in vivo (Gal4 Interaction Defective (GID) mutants). In contrast to wild-type Tra1, Tra1 GID mutants are not recruited by Gal4 to the promoter and cannot support Gal4-directed transcription activation, demonstrating that the Gal4–Tra1 interaction is required for Gal4 function. In yeast strains expressing a Tra1 GID mutant, Gal4 promoter binding is unexpectedly also diminished indicating that Gal4 and Tra1 bind cooperatively. Consistent with cooperative binding, we demonstrate that the interaction between Gal4 and Tra1 occurs predominantly on the promoter and not off DNA. Finally, we show that although Tra1 is also targeted by other activators, these interaction are unaffected by GID mutations, revealing an unanticipated specificity of the Gal4-Tra1 interaction.
2011-12-30 | GSE31389 | GEO