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    Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.

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    37
    Author
    Ferrón, SR; Radford, EJ; Domingo-Muelas, A; Kleine, I; Ramme, A; Gray, D; Sandovici, I; Constancia, M; Ward, A; Menheniott, TR; ...
    Date
    2015-09-15
    Source Title
    Nature Communications
    Publisher
    Springer Science and Business Media LLC
    University of Melbourne Author/s
    Menheniott, Trevelyan
    Affiliation
    Paediatrics (RCH)
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Ferrón, S. R., Radford, E. J., Domingo-Muelas, A., Kleine, I., Ramme, A., Gray, D., Sandovici, I., Constancia, M., Ward, A., Menheniott, T. R. & Ferguson-Smith, A. C. (2015). Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.. Nat Commun, 6 (1), pp.8265-. https://doi.org/10.1038/ncomms9265.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/260295
    DOI
    10.1038/ncomms9265
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4579569
    Abstract
    Genomic imprinting is implicated in the control of gene dosage in neurogenic niches. Here we address the importance of Igf2 imprinting for murine adult neurogenesis in the subventricular zone (SVZ) and in the subgranular zone (SGZ) of the hippocampus in vivo. In the SVZ, paracrine IGF2 is a cerebrospinal fluid and endothelial-derived neurogenic factor requiring biallelic expression, with mutants having reduced activation of the stem cell pool and impaired olfactory bulb neurogenesis. In contrast, Igf2 is imprinted in the hippocampus acting as an autocrine factor expressed in neural stem cells (NSCs) solely from the paternal allele. Conditional mutagenesis of Igf2 in blood vessels confirms that endothelial-derived IGF2 contributes to NSC maintenance in SVZ but not in the SGZ, and that this is regulated by the biallelic expression of IGF2 in the vascular compartment. Our findings indicate that a regulatory decision to imprint or not is a functionally important mechanism of transcriptional dosage control in adult neurogenesis.

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