Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis
Nature Publishing Group
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Ferrón, S., Radford, E., Domingo-Muelas, A., Kleine, I., Ramme, A., Gray, D., Sandovici, I., et al. (2015). Differential genomic imprinting regulates paracrine and autocrine roles of IGF2 in mouse adult neurogenesis. Nature Communications, 6 (8265)https://doi.org/10.1038/ncomms9265
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.
Biological sciences, Neuroscience, Genetics, Developmental biology
This work was supported by grants from Ministerio de Economía y Competitividad (SAF2012-40107), Generalitat Valenciana (Programa ACOMP2014-258) and Fundación BBVA to SRF and grants from the MRC, Wellcome Trust and EU FP7 Ingenium Training Network to AFS. AW and TRM were supported by the Association for International Cancer Research and Medical Research Council, UK.SRF was a recipient of a Herchel-Smith fellowship and currently is a Ramón y Cajal investigator. ADM is funded by a Spanish FPU fellowship program of the Ministerio de Educación, Cultura y Deporte. AR was from the Erasmus Placement Program.
Wellcome Trust (095606/Z/11/Z)
External DOI: https://doi.org/10.1038/ncomms9265
This record's URL: https://www.repository.cam.ac.uk/handle/1810/249157
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/