Browsing by Subject "Embryonic Development"

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    Comparison of pattern detection methods in microarray time series of the segmentation clock.
    (PLoS One, 2008-08-06) Dequéant, Mary-Lee; Ahnert, Sebastian; Edelsbrunner, Herbert; Fink, Thomas MA; Glynn, Earl F; Hattem, Gaye; Kudlicki, Andrzej; Mileyko, Yuriy; Morton, Jason; Mushegian, Arcady R; Pachter, Lior; Rowicka, Maga; Shiu, Anne; Sturmfels, Bernd; Pourquié, Olivier
    While genome-wide gene expression data are generated at an increasing rate, the repertoire of approaches for pattern discovery in these data is still limited. Identifying subtle patterns of interest in large amounts of data (tens of thousands of profiles) associated with a certain level of noise remains a challenge. A microarray time series was recently generated to study the transcriptional program of the mouse segmentation clock, a biological oscillator associated with the periodic formation of the segments of the body axis. A method related to Fourier analysis, the Lomb-Scargle periodogram, was used to detect periodic profiles in the dataset, leading to the identification of a novel set of cyclic genes associated with the segmentation clock. Here, we applied to the same microarray time series dataset four distinct mathematical methods to identify significant patterns in gene expression profiles. These methods are called: Phase consistency, Address reduction, Cyclohedron test and Stable persistence, and are based on different conceptual frameworks that are either hypothesis- or data-driven. Some of the methods, unlike Fourier transforms, are not dependent on the assumption of periodicity of the pattern of interest. Remarkably, these methods identified blindly the expression profiles of known cyclic genes as the most significant patterns in the dataset. Many candidate genes predicted by more than one approach appeared to be true positive cyclic genes and will be of particular interest for future research. In addition, these methods predicted novel candidate cyclic genes that were consistent with previous biological knowledge and experimental validation in mouse embryos. Our results demonstrate the utility of these novel pattern detection strategies, notably for detection of periodic profiles, and suggest that combining several distinct mathematical approaches to analyze microarray datasets is a valuable strategy for identifying genes that exhibit novel, interesting transcriptional patterns.
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    Cytoplasmic inheritance redux.
    (Adv Child Dev Behav, 2013) Charney, Evan
    Since the early twentieth century, inheritance was seen as the inheritance of genes. Concurrent with the acceptance of the genetic theory of inheritance was the rejection of the idea that the cytoplasm of the oocyte could also play a role in inheritance and a corresponding devaluation of embryology as a discipline critical for understanding human development. Development, and variation in development, came to be viewed solely as matters of genetic inheritance and genetic variation. We now know that inheritance is a matter of both genetic and cytoplasmic inheritance. A growing awareness of the centrality of the cytoplasm in explaining both human development and phenotypic variation has been promoted by two contemporaneous developments: the continuing elaboration of the molecular mechanisms of epigenetics and the global rise of artificial reproductive technologies. I review recent developments in the ongoing elaboration of the role of the cytoplasm in human inheritance and development.
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    dbl-1/TGF-β and daf-12/NHR Signaling Mediate Cell-Nonautonomous Effects of daf-16/FOXO on Starvation-Induced Developmental Arrest.
    (PLoS Genet, 2015-12) Kaplan, RE; Chen, Y; Moore, BT; Jordan, JM; Maxwell, CS; Schindler, AJ; Baugh, LR
    Nutrient availability has profound influence on development. In the nematode C. elegans, nutrient availability governs post-embryonic development. L1-stage larvae remain in a state of developmental arrest after hatching until they feed. This "L1 arrest" (or "L1 diapause") is associated with increased stress resistance, supporting starvation survival. Loss of the transcription factor daf-16/FOXO, an effector of insulin/IGF signaling, results in arrest-defective and starvation-sensitive phenotypes. We show that daf-16/FOXO regulates L1 arrest cell-nonautonomously, suggesting that insulin/IGF signaling regulates at least one additional signaling pathway. We used mRNA-seq to identify candidate signaling molecules affected by daf-16/FOXO during L1 arrest. dbl-1/TGF-β, a ligand for the Sma/Mab pathway, daf-12/NHR and daf-36/oxygenase, an upstream component of the daf-12 steroid hormone signaling pathway, were up-regulated during L1 arrest in a daf-16/FOXO mutant. Using genetic epistasis analysis, we show that dbl-1/TGF-β and daf-12/NHR steroid hormone signaling pathways are required for the daf-16/FOXO arrest-defective phenotype, suggesting that daf-16/FOXO represses dbl-1/TGF-β, daf-12/NHR and daf-36/oxygenase. The dbl-1/TGF-β and daf-12/NHR pathways have not previously been shown to affect L1 development, but we found that disruption of these pathways delayed L1 development in fed larvae, consistent with these pathways promoting development in starved daf-16/FOXO mutants. Though the dbl-1/TGF-β and daf-12/NHR pathways are epistatic to daf-16/FOXO for the arrest-defective phenotype, disruption of these pathways does not suppress starvation sensitivity of daf-16/FOXO mutants. This observation uncouples starvation survival from developmental arrest, indicating that DAF-16/FOXO targets distinct effectors for each phenotype and revealing that inappropriate development during starvation does not cause the early demise of daf-16/FOXO mutants. Overall, this study shows that daf-16/FOXO promotes developmental arrest cell-nonautonomously by repressing pathways that promote larval development.
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    Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH-adapted killifish.
    (Neurotoxicol Teratol, 2016-01) Brown, DR; Bailey, JM; Oliveri, AN; Levin, ED; Di Giulio, RT
    Acute exposures to some individual polycyclic aromatic hydrocarbons (PAHs) and complex PAH mixtures are known to cause cardiac malformations and edema in the developing fish embryo. However, the heart is not the only organ impacted by developmental PAH exposure. The developing brain is also affected, resulting in lasting behavioral dysfunction. While acute exposures to some PAHs are teratogenically lethal in fish, little is known about the later life consequences of early life, lower dose subteratogenic PAH exposures. We sought to determine and characterize the long-term behavioral consequences of subteratogenic developmental PAH mixture exposure in both naive killifish and PAH-adapted killifish using sediment pore water derived from the Atlantic Wood Industries Superfund Site. Killifish offspring were embryonically treated with two low-level PAH mixture dilutions of Elizabeth River sediment extract (ERSE) (TPAH 5.04 μg/L and 50.4 μg/L) at 24h post fertilization. Following exposure, killifish were raised to larval, juvenile, and adult life stages and subjected to a series of behavioral tests including: a locomotor activity test (4 days post-hatch), a sensorimotor response tap/habituation test (3 months post hatch), and a novel tank diving and exploration test (3months post hatch). Killifish were also monitored for survival at 1, 2, and 5 months over 5-month rearing period. Developmental PAH exposure caused short-term as well as persistent behavioral impairments in naive killifish. In contrast, the PAH-adapted killifish did not show behavioral alterations following PAH exposure. PAH mixture exposure caused increased mortality in reference killifish over time; yet, the PAH-adapted killifish, while demonstrating long-term rearing mortality, had no significant changes in mortality associated with ERSE exposure. This study demonstrated that early embryonic exposure to PAH-contaminated sediment pore water caused long-term locomotor and behavioral alterations in killifish, and that locomotor alterations could be observed in early larval stages. Additionally, our study highlights the resistance to behavioral alterations caused by low-level PAH mixture exposure in the adapted killifish population. Furthermore, this is the first longitudinal behavioral study to use killifish, an environmentally important estuarine teleost fish, and this testing framework can be used for future contaminant assessment.
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    Developmental Exposure to Low Concentrations of Organophosphate Flame Retardants Causes Life-Long Behavioral Alterations in Zebrafish.
    (Toxicological sciences : an official journal of the Society of Toxicology, 2018-10) Glazer, Lilah; Hawkey, Andrew B; Wells, Corinne N; Drastal, Meghan; Odamah, Kathryn-Ann; Behl, Mamta; Levin, Edward D
    As the older class of brominated flame retardants (BFRs) are phased out of commercial use because of findings of neurotoxicity with developmental exposure, a newer class of flame retardants have been introduced, the organophosphate flame retardants (OPFRs). Presently, little is known about the potential for developmental neurotoxicity or the behavioral consequences of OPFR exposure. Our aim was to characterize the life-long neurobehavioral effects of 4 widely used OPFRs using the zebrafish model. Zebrafish embryos were exposed to 0.1% DMSO (vehicle control); or one of the following treatments; isopropylated phenyl phosphate (IPP) (0.01, 0.03, 0.1, 0.3 µM); butylphenyl diphenyl phosphate (BPDP) (0.003, 0.03, 0.3, 3 µM); 2-ethylhexyl diphenyl phosphate (EHDP) (0.03, 0.3, 1 µM); isodecyl diphenyl phosphate (IDDP) (0.1, 0.3, 1, 10 µM) from 0- to 5-days postfertilization. On Day 6, the larvae were tested for motility under alternating dark and light conditions. Finally, at 5-7 months of age the exposed fish and controls were tested on a battery of behavioral tests to assess emotional function, sensorimotor response, social interaction and predator evasion. These tests showed chemical-specific short-term effects of altered motility in larvae in all of the tested compounds, and long-term impairment of anxiety-related behavior in adults following IPP, BPDP, or EHDP exposures. Our results show that OPFRs may not be a safe alternative to the phased-out BFRs and may cause behavioral impacts throughout the lifespan. Further research should evaluate the risk to mammalian experimental models and humans.
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    Tissue self-organization underlies morphogenesis of the notochord.
    (Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2018-09) Norman, James; Sorrell, Emma L; Hu, Yi; Siripurapu, Vaishnavi; Garcia, Jamie; Bagwell, Jennifer; Charbonneau, Patrick; Lubkin, Sharon R; Bagnat, Michel
    The notochord is a conserved axial structure that in vertebrates serves as a hydrostatic scaffold for embryonic axis elongation and, later on, for proper spine assembly. It consists of a core of large fluid-filled vacuolated cells surrounded by an epithelial sheath that is encased in extracellular matrix. During morphogenesis, the vacuolated cells inflate their vacuole and arrange in a stereotypical staircase pattern. We investigated the origin of this pattern and found that it can be achieved purely by simple physical principles. We are able to model the arrangement of vacuolated cells within the zebrafish notochord using a physical model composed of silicone tubes and water-absorbing polymer beads. The biological structure and the physical model can be accurately described by the theory developed for the packing of spheres and foams in cylinders. Our experiments with physical models and numerical simulations generated several predictions on key features of notochord organization that we documented and tested experimentally in zebrafish. Altogether, our data reveal that the organization of the vertebrate notochord is governed by the density of the osmotically swelling vacuolated cells and the aspect ratio of the notochord rod. We therefore conclude that self-organization underlies morphogenesis of the vertebrate notochord.This article is part of the Theo Murphy meeting issue on 'Mechanics of development'.
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    Use of biological detection methods to assess dioxin-like compounds in sediments of Bohai Bay, China.
    (Ecotoxicology and environmental safety, 2019-05) Dong, Wenjing; Wang, Feng; Fang, Mingliang; Wu, Jie; Wang, Shuaiyu; Li, Ming; Yang, Jingfeng; Chernick, Melissa; Hinton, David E; Pei, De-Sheng; Chen, Hongxing; Zheng, Na; Mu, Jingli; Xie, Lingtian; Dong, Wu
    Bohai Bay, in the western region of northeastern China's Bohai Sea, receives water from large rivers containing various pollutants including dioxin-like compounds (DLCs). This study used the established zebrafish (Danio rerio) model, its known developmental toxicity endpoints and sensitive molecular analyses to evaluate sediments near and around an industrial effluent site in Bohai Bay. The primary objective was to assess the efficacy of rapid biological detection methods as an addition to chemical analyses. Embryos were exposed to various concentrations of sediment extracts as well as a 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) positive control. Exposure to sediment extract nearest the discharge site (P1) resulted in the most severe- and highest rates of change in embryos and larvae, suggesting that DLC contaminated sediment probably did not occur much beyond it. P1 extract resulted in concentration dependent increases in mortality and pericardial edema. Its highest concentration caused up-regulation of P-450 (CYP)-1A1(CYP1A) mRNA expression at 72 h post fertilization (hpf), an increase in its expression in gill arches as observed by whole mount in situ hybridization, and an increased signal in the Tg(cyp1a: mCherry) transgenic line. The pattern and magnitude of response was very similar to that of TCDD and supported the presence of DLCs in these sediment samples. Follow-up chemical analysis confirmed this presence and identified H7CDF, O8CDF and O8CDD as the main components in P1 extract. This study validates the use of biological assays as a rapid, sensitive, and cost-effective method to evaluate DLCs and their effects in sediment samples. Additionally, it provides support for the conclusion that DLCs have limited remobilization capacity in marine sediments.