Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis
Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis
AbstractGenomic 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.
- Children's Hospital at Westmead Australia
- University of Cambridge United Kingdom
- Cambridge University Hospitals NHS Foundation Trust United Kingdom
- University of Bath United Kingdom
- National Institute for Health Research United Kingdom
Neurogenesis, Gene Dosage, 610, Endothelial Cells, Gene Expression Regulation, Developmental, Enzyme-Linked Immunosorbent Assay, Hippocampus, Immunohistochemistry, Olfactory Bulb, Article, Autocrine Communication, Genomic Imprinting, Mice, Neural Stem Cells, Insulin-Like Growth Factor II, Gene Knockdown Techniques, Lateral Ventricles, Paracrine Communication, Animals
Neurogenesis, Gene Dosage, 610, Endothelial Cells, Gene Expression Regulation, Developmental, Enzyme-Linked Immunosorbent Assay, Hippocampus, Immunohistochemistry, Olfactory Bulb, Article, Autocrine Communication, Genomic Imprinting, Mice, Neural Stem Cells, Insulin-Like Growth Factor II, Gene Knockdown Techniques, Lateral Ventricles, Paracrine Communication, Animals
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