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Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium.

Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. Research Abstract Details 

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  • Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. Abstract Text:

    pratheesh sathyanPratheesh Sathyan,honey b goldenHoney B Golden,rajesh c mirandaRajesh C Miranda,

    The fetal brain is sensitive to a variety of teratogens, including ethanol. We showed previously that ethanol induced mitosis and stem cell maturation, but not death, in fetal cerebral cortex-derived progenitors. We tested the hypothesis that micro-RNAs (miRNAs) could mediate the teratogenic effects of ethanol in a fetal mouse cerebral cortex-derived neurosphere culture model. Ethanol, at a level attained by alcoholics, significantly suppressed the expression of four miRNAs, miR-21, -335, -9, and -153, whereas a lower ethanol concentration, attainable during social drinking, induced miR-335 expression. A GABA(A) receptor-dependent mechanism mediated miR-21, but not miR-335 suppression, suggesting that divergent mechanisms regulate ethanol-sensitive miRNAs. Antisense-mediated suppression of miR-21 expression resulted in apoptosis, suggesting that miR-21 is an antiapoptotic factor. miR-335 knockdown promoted cell proliferation and prevented death induced by concurrently suppressing miR-21, indicating that miR-335 is a proapoptotic, antimitogenic factor whose actions are antagonistic to miR-21. Computational analyses identified two genes, Jagged-1, a Notch-receptor ligand, and embryonic-lethal abnormal vision, Drosophila-like 2 (ELAVL2), a brain-specific regulator of RNA stability, as presumptive targets of three of four ethanol-sensitive micro-RNAs. Combined knockdown of miR-335, -21, and -153 significantly increased Jagged-1 mRNA. Furthermore, ethanol induced both Jagged-1 and ELAVL2 mRNA. The collective suppression of micro-RNAs is consistent with ethanol induction of cell cycle and neuroepithelial maturation in the absence of apoptosis. These data identify a role for micro-RNAs as epigenetic intermediaries, which permit teratogens to shape complex, divergent developmental processes, and additionally demonstrate that coordinately regulated miRNAs exhibit both functional synergy and antagonism toward each other.

    Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. Publishing Authors By Initials

    p sathyanP Sathyan,hb goldenHB Golden,rc mirandaRC Miranda,

    For similar cells: stem cells research abstracts see: cells: stem cells research

    PUBMED ID PMID:

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    Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: The Journal of neuroscience : the official journal

    VOLUME: 27

    Page Numbers: 8546-57

    Journal Abbreviation: J. Neurosci.

    ISSN: 1529-2401

    DAY: 8

    MONTH: Aug

    YEAR: 2007

    Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8102140

    Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. Keywords Mesh Terms:

    KEYWORDS: Stem Cells

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium. Information

    Substance Name: Ethanol

    Registry Number: 64-17-5

    Grant and Affiliation Information for Competing interactions between micro-RNAs determine neural progenitor survival and proliferation after ethanol exposure: evidence from an ex vivo model of the fetal cerebral cortical neuroepithelium.

    AFFILIATION: Department Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M Health Science Center, Texas 77843-1114, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIAAA

    GRANT: AA13440

    ACRONYM: AA

    MEDLINETA: J Neurosci

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    ACCESSION NUMBER:

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