title: Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis.
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.
authors.affiliation: Departamento de Biología Celular, Universidad de Valencia, Dr Moliner, 50, Burjassot 46100, Spain.
authors.forename: S R
authors.initials: SR
authors.lastname: Ferrón
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Radford
authors.affiliation: Departamento de Biología Celular, Universidad de Valencia, Dr Moliner, 50, Burjassot 46100, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Domingo-Muelas
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors.forename: I
authors.initials: I
authors.lastname: Kleine
authors.affiliation: Departamento de Biología Celular, Universidad de Valencia, Dr Moliner, 50, Burjassot 46100, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Ramme
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors.forename: D
authors.initials: D
authors.lastname: Gray
authors.affiliation: Department of Obstetrics and Gynaecology, University of Cambridge, Robinson Way, Cambridge CB2 0SW, UK.|Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
authors.forename: I
authors.initials: I
authors.lastname: Sandovici
authors.affiliation: Department of Obstetrics and Gynaecology, University of Cambridge, Robinson Way, Cambridge CB2 0SW, UK.|Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.|NIHR Cambridge Biomedical Research Centre, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: M
authors.initials: M
authors.lastname: Constancia
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ward
authors.affiliation: Murdoch Children's Research Institute, Royal Children Hospital, Flemington Road, Parkville, Victoria 3052, Australia.
authors.forename: T R
authors.initials: TR
authors.lastname: Menheniott
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.|Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Ferguson-Smith
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018392:Genomic Imprinting / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D019899:Paracrine Communication / Q000235:genetics*
chemical_list: C513121:IGF2 protein, mouse; D007335:Insulin-Like Growth Factor II