Vegfa Impacts Early Myocardium Development in Zebrafish.
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ABSTRACT:
SUBMITTER: Zhu D
PROVIDER: S-EPMC5343978 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesEndocardial cushions are precursors of the valve septum complex that separates the four heart chambers. Several genes have been implicated in the development of endocardial cushions. Specifically, ERp44 has been found to play a role in the early secretory pathway, but its function in heart development has not been well studied.Materials and methodsIn this study, we established conditional and tissue-specific knockout mouse models. The morphology, survival rate, the development of heart and endocardial cushion were under evaluation. The relationship between ERp44 and VEGFA was investigated by transcriptome, qPCR, WB, immunofluorescence and immunohistochemistry.ResultsERp44 knockout (KO) mice were smaller in size, and most mice died during early postnatal life. KO hearts exhibited the typical phenotypes of congenital heart diseases, such as abnormal heart shapes and severe septal and valvular defects. Similar phenotypes were found in cTNT-Cre+/- ; ERp44fl / fl mice, which indicated that myocardial ERp44 principally controls endocardial cushion formation. Further studies demonstrated that the deletion of ERp44 significantly decreased the proliferation of cushion cells and impaired the endocardial-mesenchymal transition (EndMT), which was followed by endocardial cushion dysplasia. Finally, we found that ERp44 was directly bound to VEGFA and controlled its release, further regulating EndMT.ConclusionWe demonstrated that ERp44 plays a specific role in heart development. ERp44 contributes to the development of the endocardial cushion by affecting VEGFA-mediated EndMT.
| S-EPMC8891561 | biostudies-literature
Project description:BACKGROUND: The transition from fertilized egg to embryo is accompanied by a multitude of changes in gene expression, and the transcriptional events that underlie these processes have not yet been fully characterized. In this study RNA-Seq is used to compare the transcription profiles of four early developmental stages in zebrafish (Danio rerio) on a global scale. RESULTS: An average of 79 M total reads were detected from the different stages. Out of the total number of reads 65% - 73% reads were successfully mapped and 36% - 44% out of those were uniquely mapped. The total number of detected unique gene transcripts was 11187, of which 10096 were present at 1-cell stage. The largest number of common transcripts was observed between 1-cell stage and 16-cell stage. An enrichment of gene transcripts with molecular functions of DNA binding, protein folding and processing as well as metal ion binding was observed with progression of development. The sequence data (accession number ERP000635) is available at the European Nucleotide Archive. CONCLUSION: Clustering of expression profiles shows that a majority of the detected gene transcripts are present at steady levels, and thus a minority of the gene transcripts clusters as increasing or decreasing in expression over the four investigated developmental stages. The three earliest developmental stages were similar when comparing highly expressed genes, whereas the 50% epiboly stage differed from the other three stages in the identity of highly expressed genes, number of uniquely expressed genes and enrichment of GO molecular functions. Taken together, these observations indicate a major transition in gene regulation and transcriptional activity taking place between the 512-cell and 50% epiboly stages, in accordance with previous studies.
| S-EPMC3118190 | biostudies-literature
Project description:The mechanisms underlying organ vascularization are not well understood. The zebrafish intestinal vasculature forms early, is easily imaged using transgenic lines and in-situ hybridization, and develops in a stereotypical pattern thus making it an excellent model for investigating mechanisms of organ specific vascularization. Here, we demonstrate that the sub-intestinal vein (SIV) and supra-intestinal artery (SIA) form by a novel mechanism from angioblasts that migrate out of the posterior cardinal vein and coalesce to form the intestinal vasculature in an anterior to posterior wave with the SIA forming after the SIV. We show that vascular endothelial growth factor aa (vegfaa) is expressed in the endoderm at the site where intestinal vessels form and therefore likely provides a guidance signal. Vegfa/Vegfr2 signaling is required for early intestinal vasculature development with mutation in vegfaa or loss of Vegfr2 homologs causing nearly complete inhibition of the formation of the intestinal vasculature. Vegfc and Vegfr3 function, however, are dispensable for intestinal vascularization. Interestingly, ubiquitous overexpression of Vegfc resulted in an overgrowth of the SIV, suggesting that Vegfc is sufficient to induce SIV development. These results argue that Vegfa signaling directs endothelial cells to migrate out of existing vasculature and coalesce to form the intestinal vessels. It is likely that a similar mechanism is utilized during vascularization of other organs.
| S-EPMC4769896 | biostudies-literature
Project description:Gene expression profiling of zebrafish early eye development on 3 to 5 days post fertilization (dpf) Gene expression on 3 to 5 dpf eyes were compared. Each sample contains three replicates.
2012-12-31 | E-GEOD-19320 | biostudies-arrayexpress
Project description:IntroductionEmbryonic exposure to ethanol leads to a condition of physical, behavioral, and cognitive deficiencies named fetal alcohol spectrum disorders (FASD). The most severe variations are in fetal alcohol syndrome (FAS), which is easier to diagnose and not studied in animal models. On the other side, the pFAS (partial fetal alcohol syndrome) includes cases of alcohol-related congenital disabilities and neurodevelopmental disorder with an inconclusive diagnosis. In recent years, the zebrafish has become a valuable model to study FASD and its variations.MethodsThis study characterizes the zebrafish embryonic and larval development after low and moderate ethanol concentration exposure. Fish eggs were exposed to 0.0%, 0.25%, 0.5%, and 1.0% ethanol at 24 hr postfertilization, and embryonic development was observed every 8 hr up to 120 hpf. It evaluated movements, phenotypic abnormalities, hatching, cardiac function and heartbeat frequency, larvae length at 120 hpf, and the apoptotic cells' fluorescence stained with acridine orange.ResultsEmbryonic exposure to 0.5% and 1% ethanol presented reduced body size, decreased heartbeat rate, higher numbers of apoptotic cells, and hatching time differences.ConclusionsOur results suggest any ethanol exposure during embryogenesis can be harmful and reinforces zebrafish as a suitable model for fetal alcohol spectrum disorders (FASD).
| S-EPMC8213935 | biostudies-literature
Project description:BackgroundThe MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of MVD gene remains largely unknown. Therefore, we analyzed the function of mvda gene, orthologous to the human MVD gene, in developing zebrafish.MethodsMorpholino antisense oligonucleotide technique was used to generate mvda loss-of-function phenotypes. Knockdown of mvda was confirmed by RT-PCR and Sanger sequencing. Scanning and transmission electron microscopy were performed to analyze the morphology of the epidermis. Angiogenesis study was presented using the Tg(fli1a:EGFP)y1 transgenic strain. In addition, acridine orange staining was used to examine the apoptotic cells in vivo.ResultsAs expected, the mvda morphants showed abnormal morphology of the epidermis. Moreover, we observed ectopic sprouts in trunk angiogenesis and impaired formation of the caudal vein plexus in the mvda-deficient zebrafish. Besides, increased apoptosis was found throughout the tail, heart, and eyes in mvda zebrafish morphants.ConclusionsThese findings indicated the essential role of mvda in the early development of zebrafish. This was the first in vivo knockdown study of the zebrafish mvda gene, which might offer insight into the biological function of the human MVD gene.
| S-EPMC8164810 | biostudies-literature
Project description:Gene expression profiling of zebrafish early eye development on 3 to 5 days post fertilization (dpf)
2012-12-31 | GSE19320 | GEO
Project description:Vascular endothelial growth factor A (VEGFA) and the type III receptor tyrosine kinase receptors (RTKs) are both required for the differentiation of endothelial cells (vasculogenesis) and for the sprouting of new capillaries (angiogenesis). We have isolated a duplicated zebrafish VegfA locus, termed VegfAb, and a duplicate RTK locus with homology to KDR/FLK1 (named Kdrb). Morpholino-disrupted VegfAb embryos develop a normal circulatory system until approximately 2 to 3 days after fertilization (dpf), when defects in angiogenesis permit blood to extravasate into many tissues. Unlike the VegfAa(121) and VegfAa(165) isoforms, the VegfAb isoforms VegfAb(171) and VegfAb(210) are not normally secreted when expressed in mammalian tissue culture cells. The Kdrb locus encodes a 1361-amino acid transmembrane receptor with strong homology to mammalian KDR. Combined knockdown of both RTKs leads to defects in vascular development, suggesting that they cooperate in mediating the vascular effects of VegfA in zebrafish development. Both VegfAa and VegfAb can individually bind and promote phosphorylation of both Flk1 (Kdra) and Kdrb proteins in vitro. Taken together, our data support a model in the zebrafish, in which duplicated VegfA and multiple type III RTKs mediate vascular development.
| S-EPMC2077312 | biostudies-literature
Project description:The rapid deployment of 5G spectrum by the telecommunication industry is intended to promote better connectivity and data integration among various industries. However, since exposures to radio frequency radiations (RFR) >2.4 GHz are still uncommon, concerns about their potential health impacts are ongoing. In this study, we used the embryonic zebrafish model to assess the impacts of a 3.5 GHz RFR on biology- a frequency typically used by 5G-enabled cell phones and lies within the 4G and 5G bandwidth. We established a plate-based exposure setup for RFRs, exposed developing zebrafish to 3.5 GHz RFR, specific absorption rate (SAR) ≈ 8.27 W/Kg from 6 h post fertilization (hpf) to 48 hpf, and measured a battery of morphological and behavioral endpoints at 120 hpf. Our results revealed no significant impacts on mortality, morphology or photomotor response and a modest inhibition of startle response suggesting some levels of sensorimotor disruptions. This suggests that the cell phone radiations at low GHz-level frequencies are likely benign, with subtle sensorimotor effects. Through this assessment, we have established a robust setup for zebrafish RFR exposures readily amenable to testing various powers and frequencies. Future developmental exposure studies in zebrafish will evaluate a wider portion of the radio frequency spectrum to discover the bioactive regions, the potential molecular targets of RFR and the potential long-term effects on adult behavior.
| S-EPMC7347199 | biostudies-literature
Project description:PurposeTo assess human fertilization and preimplantation embryo development in the presence and in the absence of carbon filtrationMethodsThis is a retrospective cohort analysis of fresh, controlled ovarian hyperstimulation cycles as well as previously cryopreserved pronuclear stage embryo transfer cycles in a single IVF center. Embryo development and cycle-based outcomes were compared among three groups: 1) when carbon filtration was present, 2) when carbon filtration was absent, and 3) when carbon filtration had been restored.ResultsA total of 524 fresh cycles and 156 cryopreserved embryo cycles were analyzed. Fertilization, cleavage, and blastocyst conversion rates for fresh cycles all declined during the period of absent carbon filtration and recovered after the restoration of carbon filtration. Cryopreserved embryos that were thawed and cultured during the period of absent filtration did not have changes in cleavage or blastocyst conversion rates compared to periods where carbon filtration was present. Clinical pregnancy and live birth rates were unchanged among the three time periods.ConclusionsThe absence of carbon filtration in an IVF laboratory air handler is associated with poor fertilization and early embryo development for fresh cycles. Because development of previously frozen pronuclear stage embryos was unaffected, the lack of carbon filtration may preferentially affect embryos in the peri-fertilization period. Carbon filtration is an integral part to a successful human in-vitro fertilization laboratory.
| S-EPMC4531868 | biostudies-literature