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Nat Commun ; 6: 8265, 2015 Sep 15.
Article in English | MEDLINE | ID: mdl-26369386

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.


Subject(s)
Autocrine Communication/genetics , Genomic Imprinting/genetics , Hippocampus/metabolism , Insulin-Like Growth Factor II/genetics , Lateral Ventricles/metabolism , Neural Stem Cells/metabolism , Neurogenesis/genetics , Paracrine Communication/genetics , Animals , Endothelial Cells/metabolism , Enzyme-Linked Immunosorbent Assay , Gene Dosage , Gene Expression Regulation, Developmental , Gene Knockdown Techniques , Hippocampus/cytology , Immunohistochemistry , Lateral Ventricles/cytology , Mice , Neural Stem Cells/cytology , Olfactory Bulb/cytology , Olfactory Bulb/metabolism
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