Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis
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 cerebro...
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Published in | Nature communications Vol. 6; no. 1; p. 8265 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
15.09.2015
Nature Publishing Group Nature Pub. Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
Selective biallelic expression of certain genes through genomic imprinting are known to play a role in controlling neurogenesis in the adult mammalian brain. Here the authors investigate the role of imprinting in the dosage control of Igf2 and its relevance for the function of IGF2 as a neurogenic regulator in the mouse brain. |
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Bibliography: | These authors contributed equally to this work. |
ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/ncomms9265 |