IGF2BP1 is required for hepatic outgrowth during early liver development in zebrafish
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ABSTRACT:
PROVIDER: PRJNA554693 | ENA |
REPOSITORIES: ENA
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Project description:IGF2BPs, a subclass of RNA-binding proteins, regulate cellular differentiation, proliferation and migration during mutiple organs development, but its function still remains unclear. Here, we provide the in vivo evidence that Igf2bp1 is pivotal during liver development by using zebrafish as a model organism. Whole-mount in situ hybridization showed that igf2bp1 was highly expressed in liver, and the morpholino knockdown had no effect on hepatoblast differentiation, but the liver size was significantly reduced. Data from microarray analysis indicated that the hepatic outgrowth defect in igf2bp1 konckdown embroys could be attributed to the significantly down-regulated of several important genes related to liver development, such as epo, cxcl8, socs1a, uox, ripk1, itgb1 and arhgef7. Besides, the igf2bp1Δ5 mutant, obtained by CRISPR/Cas9, showed the same phenotype with morpholino knockdown. Altogether, our researchs demonstrate that Igf2bp1 is a critical regulator during liver development by modulating several genes related to hepatic outgrowth.
2021-07-01 | GSE134318 | GEO
Project description:Regulation of embryonic liver growth remains largely elusive. Progranulin has been discussed in pathological liver growth; however, the functional role of Pgrn in embryonic liver growth has never been addressed. Knockdown of GrnA, the orthologue of mammalian pgrn in zebrafish, displayed a deficient hepatic outgrowth during hepatogenesis. Expression profiles manifested that pgrn-deficiency impaired hepatogenesis associated with dysregulation of Met signaling. Pgrn regulates hepatic expression of Met was further verified in vitro and in vivo. These results indicate that Pgrn is a novel factor required for embryonic hepatic outgrowth and reveal a novel link between Pgrn and Met signaling. To explore the GrnA induced genomic responses during hepatic outgrowth, mRNA expression profiles were compared from grnA morphants and control embryos using zebrafish 14K oligonucleotide microarray at 72 hpf, when hepatocytes were rapid proliferating.
2010-11-10 | E-GEOD-19211 | biostudies-arrayexpress
Project description:Attractive growth cone turning requires Igf2bp1-dependent local translation of β-actin mRNA in response to external cues in vitro. While in vivo studies have shown that Igf2bp1 is required for cell migration and axon terminal branching, a requirement for Igf2bp1 function during axon outgrowth has not been demonstrated. Using a timelapse assay in the zebrafish retinotectal system, we demonstrate that the β-actin 3'UTR is sufficient to target local translation of the photoconvertible fluorescent protein Kaede in growth cones of pathfinding retinal ganglion cells (RGCs) in vivo. Igf2bp1 knockdown reduced RGC axonal outgrowth and tectal coverage and retinal cell survival. RGC-specific expression of a phosphomimetic Igf2bp1 reduced the density of axonal projections in the optic tract while sparing RGCs, demonstrating for the first time that Igf2bp1 is required during axon outgrowth in vivo. Therefore, regulation of local translation mediated by Igf2bp proteins may be required at all stages of axon development.
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Project description:Regulation of embryonic liver growth remains largely elusive. Progranulin has been discussed in pathological liver growth; however, the functional role of Pgrn in embryonic liver growth has never been addressed. Knockdown of GrnA, the orthologue of mammalian pgrn in zebrafish, displayed a deficient hepatic outgrowth during hepatogenesis. Expression profiles manifested that pgrn-deficiency impaired hepatogenesis associated with dysregulation of Met signaling. Pgrn regulates hepatic expression of Met was further verified in vitro and in vivo. These results indicate that Pgrn is a novel factor required for embryonic hepatic outgrowth and reveal a novel link between Pgrn and Met signaling.
2010-11-10 | GSE19211 | GEO
Project description:Our study demonstrated that the expression of Igf2bp1 in activated microglia was significantly up-regulated, implying a role of Igf2bp1 in LPS-induced m6A modifications in microglia. To understand the roles of Igf2bp1 on LPS-induced m6A modification in microglia, we performed Igf2bp1 loss-of-function (LOF) approach. Microglia stimulated by LPS were transfected with either scrambled siRNA control or Igf2bp1 siRNA for 48 hours. To m6A modification profiles in control and Igf2bp1 LOF microglia were determined by MeRIP-seq analysis.
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Project description:During development, inhibitor of DNA binding (Id) proteins, a subclass of the helix-loop-helix family of proteins, regulate cellular proliferation, differentiation, and apoptosis in various organs. However, a functional role of Id2a in liver development has not yet been reported. Here, using zebrafish as a model organism, we provide in vivo evidence that Id2a regulates hepatoblast proliferation and cell death during liver development. Initially, in the liver, id2a is expressed in hepatoblasts and after their differentiation, id2a expression is restricted to biliary epithelial cells. id2a knockdown in zebrafish embryos had no effect on hepatoblast specification or hepatocyte differentiation. However, liver size was greatly reduced in id2a morpholino-injected embryos, indicative of a hepatic outgrowth defect attributable to the significant decrease in proliferating hepatoblasts concomitant with the significant increase in hepatoblast cell death. Altogether, these data support the role of Id2a as an important regulator of hepatic outgrowth via modulation of hepatoblast proliferation and survival during liver development in zebrafish.
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Project description:We generate a single cell transcriptome dataset to characterize zebrafish fin regenerative outgrowth and explore coordinated cell behaviors.
2023-07-21 | GSE216359 | GEO
Project description:Post-transcriptional regulation mediated by RNA binding proteins is crucial for male germline development. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), an RNA binding protein, is specifically expressed in human and mouse male gonads and is involved in manifold biological processes and tumorigenesis. However, the function of IGF2BP1 in mammalian spermatogenesis remains poorly understood. Herein, we generated an Igf2bp1 conditional knockout mouse model using Nanos3-Cre. Germ cell deficiency of Igf2bp1 in mice caused spermatogenic defects in an age-dependent manner, resulting in decreased numbers of undifferentiated spermatogonia and increased germ cell apoptosis. Immunoprecipitation-mass spectrometry analysis revealed that ELAV-like RNA binding protein 1, a well-recognized mRNA stabilizer, interacted with IGF2BP1. Single cell RNA-sequencing showed distinct mRNA profiles in spermatogonia from conditional knockout versus wide type mice. Further research showed that IGF2BP1 plays a vital role in the modulation of spermatogenesis by regulating Lin28a mRNA, which is essential for clonal expansion of undifferentiated spermatogonia. Thus, our results highlight the crucial effects of IGF2BP1 on spermatogonia for the long-term maintenance of spermatogenesis
2024-09-03 | GSE276205 | GEO
Project description:UHRF1 (Ubiquitin-like, containing PHD and RING finger domains, 1) recruits DNMT1 to hemimethylated DNA during replication, is essential for maintaining DNA methylation patterns during cell division and is suggested to direct additional repressive epigenetic marks. Uhrf1 mutation in zebrafish results in multiple embryonic defects including failed hepatic outgrowth, but the epigenetic basis of these phenotypes is not known. We find that DNA methylation is the only epigenetic mark that is depleted in uhrf1 mutants and make the surprising finding that despite the reduced organ size in uhrf1 mutants, genes regulating DNA replication and S-phase progression were highly upregulated. Further, there is a striking increase in BrdU incorporation in uhrf1 mutant cells, and they retained BrdU labeling over several days, indicating they are arrested in S-phase. Moreover, some of the label retaining nuclei co-localized with TUNEL positive nuclei, suggesting that arrested cells are responsible for apoptosis. Importantly, dnmt1 mutation phenocopies the S-phase arrest and hepatic outgrowth defects in uhrf1 mutants and Dnmt1 knock-down enhances the uhrf1 hepatic phenotype. Together, these data indicate that DNA hypomethylation is sufficient to generate the uhrf1 mutant phenotype by promoting an S-phase arrest. We thus propose that cell cycle arrest is a mechanism to restrict propagation of epigenetically deranged cells during embryogenesis. Genome-wide expression profiling was performed on 2 uhrf1 mutant and 2 wildtype zebrafish larvae (120 hours post fertilization) by using Zebrafish Genome Array (Affymetrix) according to manufacturer's instruction.
2015-02-09 | E-GEOD-55339 | biostudies-arrayexpress
Project description:In this project we aim to identify phosphorylation sites of IGF2BP1 that have not been discovered yet in mass spec experiments due to insufficient coverage. To this end we used Pro-Alanase treatment that produced detectable peptides in regions that are not covered by commonly used approaches. IGF2BP1 phosphorylation was investigated in vitro by treating purified IGF2BP1 with Src and in vivo by comparing immunoprecipitated IGF2BP1 from unstressed and stressed (1.5 h thapsigargin or 2 h or arsenite) HEK293T cells expressing GFP-labeled IGF2BP1.
2024-11-13 | PXD056497 | Pride