6533b834fe1ef96bd129d21c
RESEARCH PRODUCT
Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis
S. R. FerrónE. J. RadfordA. Domingo-muelasI. KleineA. RammeD. GrayI. SandoviciM. ConstanciaA. WardT. R. MenheniottA. C. Ferguson-smithsubject
animal structuresendocrine system diseasesNeurogenesisGene DosageEndothelial CellsGene Expression Regulation DevelopmentalEnzyme-Linked Immunosorbent AssayHippocampusImmunohistochemistryOlfactory Bulbfemale genital diseases and pregnancy complicationsArticleAutocrine CommunicationGenomic ImprintingMicenervous systemNeural Stem CellsInsulin-Like Growth Factor IIGene Knockdown TechniquesLateral VentriclesParacrine CommunicationAnimalsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-09-01 | Nature Communications |