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

Author

Listed:
  • S. R. Ferrón

    (Universidad de Valencia)

  • E. J. Radford

    (University of Cambridge)

  • A. Domingo-Muelas

    (Universidad de Valencia)

  • I. Kleine

    (University of Cambridge)

  • A. Ramme

    (Universidad de Valencia)

  • D. Gray

    (University of Cambridge)

  • I. Sandovici

    (University of Cambridge
    Centre for Trophoblast Research, University of Cambridge)

  • M. Constancia

    (University of Cambridge
    Centre for Trophoblast Research, University of Cambridge
    NIHR Cambridge Biomedical Research Centre)

  • A. Ward

    (University of Bath)

  • T. R. Menheniott

    (Murdoch Children’s Research Institute, Royal Children Hospital)

  • A. C. Ferguson-Smith

    (University of Cambridge
    Centre for Trophoblast Research, University of Cambridge)

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.

Suggested Citation

  • S. R. Ferrón & E. J. Radford & A. Domingo-Muelas & I. Kleine & A. Ramme & D. Gray & I. Sandovici & M. Constancia & A. Ward & T. R. Menheniott & A. C. Ferguson-Smith, 2015. "Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9265
    DOI: 10.1038/ncomms9265
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    Cited by:

    1. Norman L. Lehman & Nathalie Spassky & Müge Sak & Amy Webb & Cory T. Zumbar & Aisulu Usubalieva & Khaled J. Alkhateeb & Joseph P. McElroy & Kirsteen H. Maclean & Paolo Fadda & Tom Liu & Vineela Gangala, 2022. "Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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