Browsing by Subject "Developmental neurobiology"

Now showing 1 - 4 of 4
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    A Biomarker Characterizing Neurodevelopment with applications in Autism
    (Nature Publishing Group, 2018-01-12) Wu, Di; José, Jorge V.; Nurnberger, John I., Jr.; Torres, Elizabeth B.; Medicine, School of Medicine
    Despite great advances in neuroscience and genetic studies, our understanding of neurodevelopmental disorders is still quite limited. An important reason is not having objective psychiatric clinical tests. Here we propose a quantitative neurodevelopment assessment by studying natural movement outputs. Movement is central to behaviors: It involves complex coordination, temporal alterations, and precise dynamic controls. We carefully analyzed the continuous movement output data, collected with high definition electromagnetic sensors at millisecond time scales. We unraveled new metrics containing striking physiological information that was unseen neither by using traditional motion assessments nor by naked eye observations. Our putative biomarker leads to precise individualized classifications. It illustrates clear differences between Autism Spectrum Disorder (ASD) subjects from mature typical developing (TD) individuals. It provides an ASD complementary quantitative classification, which closely agrees with the clinicaly assessed functioning levels in the spectrum. It also illustrates TD potential age-related neurodevelopmental trajectories. Applying our movement biomarker to the parents of the ASD individuals studied in the cohort also shows a novel potential familial signature ASD tie. This paper proposes a putative behavioral biomarker to characterize the level of neurodevelopment with high predicting power, as illustrated in ASD subjects as an example.
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    Expression of histone deacetylase enzymes in murine and chick optic nerve
    (2013) Tiwari, Sarika; Belecky-Adams, Teri; Meyer, Jason S.; Marrs, James; Atkinson, Simon
    Epigenetic alterations have been shown to control cell type specification and differentiation leading to the changes in chromatin structure and organization of many genes. HDACs have been well documented to play an important role in both neurogenesis and gliogenesis in ganglionic eminence and cortex-derived cultures. However, the role of HDACs in glial cell type specification and differentiation in the optic nerve has not been well described. As a first step towards understanding their role in glial cell type specification, we have examined histone acetylation and methylation levels as well as the expression levels and patterns of the classical HDACs in both murine and chick optic nerve. Analysis of mRNA and protein levels in the developing optic nerve indicated that all 11 members of the classical HDAC family were expressed, with a majority declining in expression as development proceeded. Based on the localization pattern in both chick and murine optic nerve glial cells, we were able to group the classical HDACs: predominantly nuclear, nuclear and cytoplasmic, predominantly cytoplasmic. Nuclear expression of HDACs during different stages of development studied in this project in both murine and chick optic nerve glial cells suggests that HDACs play a role in stage-dependent changes in gene expression that accompany differentiation of astrocytes and oligodendrocytes. Examination of localization pattern of the HDACs is the first step towards identifying the specific HDACs involved directly in specification and differentiation of glia in optic nerve.
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    The function of ASCL1 in pregnancy-induced maternal liver growth
    (2014) Lee, Joonyong; Dai, Guoli; Belecky-Adams, Teri; Meyer, Jason S.
    The maternal liver shows marked growth during pregnancy to accommodate the development and metabolic needs of the placenta and fetus. Previous study has shown that the maternal liver grows proportionally to the increase in body weight during gestation by hyperplasia and hypertrophy of hepatocytes. As the maternal liver is enlarged, the transcript level of Ascl1, a transcription factor essential to progenitor cells of the central nervous system and peripheral nervous system, is highly upregulated. The aims of the study were to (1) identify hepatic Ascl1-expressing cells, and (2) study the functions of Ascl1 in maternal liver during pregnancy. In situ hybridization shows that most cell types (parenchymal, nonparenchymal, and mesothelial cells) express Ascl1 mRNA in maternal livers during gestation and in male regenerating livers. Notably, hepatic mesothelial cells abundantly express Ascl1 during pregnancy and liver regeneration. Inducible ablation of Ascl1 gene during pregnancy results in maternal liver enlargement, litter size reduction, and fetal growth retardation. In addition, maternal hepatocytes deficient in Ascl1 gene lack majority of their cytosols and exhibit β-catenin nuclear translocation, while maintaining their cellular boundary and identity. In summary, in both maternal liver during pregnancy and regenerating liver, the expression of Ascl1 is induced in most cell types. Mesothelial cells are potential origin of Ascl1-expressing cells. Ascl1 gene is essential for the progression of normal pregnancy
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    Identification and characterization of Ascl1-expressing cells in maternal liver during pregnancy
    (2014-08-01) Kumar, Sudhanshu; Dai, Guoli; Belecky-Adams, Teri; Meyer, Jason S.
    During pregnancy, maternal liver exhibits robust growth to meet the metabolic demands of the developing placenta and fetus. Although hepatocyte hypertrophy and hyperplasia are seen in the maternal liver, the molecular and cellular mechanisms mediating the maternal hepatic adaptations to pregnancy is poorly understood. Previous microarray analysis revealed a most upregulated gene named Ascl1, a transcription factor essential for neural development, in the maternal liver at mid-gestation. The aims of the study were to (1) validate the activation of Ascl1 gene; (2) identify Ascl1-expressing cells; and (3) determine the fate of Ascl1-expressing cells, in the maternal liver during the course of gestation. Timed pregnancy was setup in mice and the maternal livers were collected at various stages of gestation. Maternal hepatic Ascl1 mRNA expression was evaluated by qRT-PCR and northern blotting. The results demonstrated that the transcript level of maternal hepatic Ascl1 is exponentially increased during the second half of pregnancy in comparison with a non-pregnant state. Using a Ascl1-GFP mouse model generated by others to monitor the behavior of neural progenitor cells, we found that maternal hepatic Ascl1-expressing cells are non-parenchymal cells, very small in size, and expanding during pregnancy. To map the fate of this cell population, we generated an in vivo tracing mouse model named Ascl1-CreERT2/ROSA26-LacZ. Using this model, we permanently labeled maternal hepatic Ascl1-expressing cells at midgestation by giving tamoxifen and analyzed the labeled cells in the maternal liver prior to parturition. We observed that the initial small Ascl1-expressing cells undergoing expansion at mid-gestation eventually became hepatocyte-like cells at the end stage of pregnancy. Taken together, our findings strongly suggest that Ascl1-expressing cells represent a novel population of hepatic progenitor cells and they can differentiate along hepatocyte lineage and contribute to pregnancy-induced maternal liver growth. Further studies are needed to firmly establish the nature and property of maternal hepatic Ascl1-expressing cells. At this stage, we have gained significant insights into the cellular mechanism by which the maternal liver adapts to pregnancy.