School of BioSciences - Research Publications
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ItemNo Preview AvailableMarsupials have monoallelic MEST expression with a conserved antisense lncRNA but MEST is not imprinted(SPRINGERNATURE, 2024-01)The imprinted isoform of the Mest gene in mice is involved in key mammalian traits such as placental and fetal growth, maternal care and mammary gland maturation. The imprinted isoform has a distinct differentially methylated region (DMR) at its promoter in eutherian mammals but in marsupials, there are no differentially methylated CpG islands between the parental alleles. Here, we examined similarities and differences in the MEST gene locus across mammals using a marsupial, the tammar wallaby, a monotreme, the platypus, and a eutherian, the mouse, to investigate how imprinting of this gene evolved in mammals. By confirming the presence of the short isoform in all mammalian groups (which is imprinted in eutherians), this study suggests that an alternative promoter for the short isoform evolved at the MEST gene locus in the common ancestor of mammals. In the tammar, the short isoform of MEST shared the putative promoter CpG island with an antisense lncRNA previously identified in humans and an isoform of a neighbouring gene CEP41. The antisense lncRNA was expressed in tammar sperm, as seen in humans. This suggested that the conserved lncRNA might be important in the establishment of MEST imprinting in therian mammals, but it was not imprinted in the tammar. In contrast to previous studies, this study shows that MEST is not imprinted in marsupials. MEST imprinting in eutherians, therefore must have occurred after the marsupial-eutherian split with the acquisition of a key epigenetic imprinting control region, the differentially methylated CpG islands between the parental alleles.
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ItemDiffusion and distal linkages govern interchromosomal dynamics during meiotic prophase.(Proceedings of the National Academy of Sciences, 2022-03-22)SignificanceEssential for sexual reproduction, meiosis is a specialized cell division required for the production of haploid gametes. Critical to this process are the pairing, recombination, and segregation of homologous chromosomes (homologs). While pairing and recombination are linked, it is not known how many linkages are sufficient to hold homologs in proximity. Here, we reveal that random diffusion and the placement of a small number of linkages are sufficient to establish the apparent "pairing" of homologs. We also show that colocalization between any two loci is more dynamic than anticipated. Our study provides observations of live interchromosomal dynamics during meiosis and illustrates the power of combining single-cell measurements with theoretical polymer modeling.
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ItemRiboceine Rescues Auranofin-Induced Craniofacial Defects in Zebrafish(MDPI, 2021-12)Craniofacial abnormalities are a common group of congenital developmental disorders that can require intensive oral surgery as part of their treatment. Neural crest cells (NCCs) contribute to the facial structures; however, they are extremely sensitive to high levels of oxidative stress, which result in craniofacial abnormalities under perturbed developmental environments. The oxidative stress-inducing compound auranofin (AFN) disrupts craniofacial development in wildtype zebrafish embryos. Here, we tested whether the antioxidant Riboceine (RBC) rescues craniofacial defects arising from exposure to AFN. RBC rescued AFN-induced cellular apoptosis and distinct defects of the cranial cartilage in zebrafish larvae. Zebrafish embryos exposed to AFN have higher expression of antioxidant genes gstp1 and prxd1, with RBC treatment partially rescuing these gene expression profiles. Our data suggest that antioxidants may have utility in preventing defects in the craniofacial cartilage owing to environmental or genetic risk, perhaps by enhancing cell survival.
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ItemChlorogenic Acid Supplementation Benefits Zebrafish Embryos Exposed to Auranofin.(MDPI AG, 2020-12-11)Antioxidant supplementation may potentially be beneficial for embryonic development to reduce complications associated with increased levels of oxidative stress. Chlorogenic acid, one of the key polyphenolic antioxidants in S. oleraceus, was evaluated for potential protective effects during embryonic development of zebrafish exposed to the teratogen auranofin. Zebrafish embryos were transiently exposed to auranofin to induce developmental abnormalities. Phenotypic abnormalities were scored based on their severity at day 5 post-fertilization. The embryos supplemented with 250 µM chlorogenic acid showed a significantly lower score in phenotypic abnormalities compared to non-supplemented embryos after auranofin exposure. Therefore, supplementation with a low dose of chlorogenic acid showed a protective effect from auranofin-induced deformities and encouraged normal growth in zebrafish embryos. This study provides further support for the potential of using antioxidant supplementation during embryonic development for protection against malformation.
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ItemDietary Intake Influences Adult Fertility and Offspring Fitness in Zebrafish(PUBLIC LIBRARY SCIENCE, 2016-11-21)The burden of malnutrition, including both over- and undernutrition, is a major public health concern. Here we used a zebrafish model of diet-induced obesity to analyze the impact of dietary intake on fertility and the phenotype of the next generation. Over an eight-week period, one group received 60 mg of food each day (60 mg arm), while another received 5 mg (5 mg arm). At the end of the diet, the body mass index of the 60 mg arm was 1.5 fold greater than the 5 mg arm. The intervention also had a marked impact on fertility; breeding success and egg production in the 60 mg arm were increased 2.1- and 6.2-fold compared to the 5 mg arm, respectively. Transcriptome analysis of eggs revealed that transcripts involved in metabolic biological processes differed according to dietary intake. The progeny from the differentially fed fish were more likely to survive when the parents had access to more food. An intergenerational crossover study revealed that while parental diet did not influence weight gain in the offspring, the progeny of well-fed parents had increased levels of physical activity when exposed again to high nutrient availability. We conclude that dietary intake has an important influence on fertility and the subsequent fitness of offspring, even prior to breeding.
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ItemEmbryonic oxidative stress results in reproductive impairment for adult zebrafish(ELSEVIER, 2015-12)Exposure to environmental stressors during embryo development can have long-term effects on the adult organism. This study used the thioredoxin reductase inhibitor auranofin to investigate the consequences of oxidative stress during zebrafish development. Auranofin at low doses triggered upregulation of the antioxidant genes gstp1 and prdx1. As the dose was increased, acute developmental abnormalities, including cerebral hemorrhaging and jaw malformation, were observed. To determine whether transient disruption of redox homeostasis during development could have long-term consequences, zebrafish embryos were exposed to a low dose of auranofin from 6-24 hours post fertilization, and then raised to adulthood. The adult fish were outwardly normal in their appearance with no gross physical differences compared to the control group. However, these adult fish had reduced odds of breeding and a lower incidence of egg fertilization. This study shows that a suboptimal early life environment can reduce the chances of reproductive success in adulthood.